Identification

Name
alpha-Tocopherol acetate
Accession Number
DB14003
Type
Small Molecule
Groups
Approved
Description

Alpha-tocopherol is the primary form of vitamin E that is preferentially used by the human body to meet appropriate dietary requirements. In particular, the RRR-alpha-tocopherol (or sometimes called the d-alpha-tocopherol stereoisomer) stereoisomer is considered the natural formation of alpha-tocopherol and generally exhibits the greatest bioavailability out of all of the alpha-tocopherol stereoisomers. Moreover, RRR-alpha-tocopherol acetate is a relatively stabilized form of vitamin E that is most commonly used as a food additive when needed [2].

Alpha-tocopherol acetate is subsequently most commonly indicated for dietary supplementation in individuals who may demonstrate a genuine deficiency in vitamin E. Vitamin E itself is naturally found in various foods, added to others, or used in commercially available products as a dietary supplement. The recommended dietary allowances (RDAs) for vitamin E alpha-tocopherol are: males = 4 mg (6 IU) females = 4 mg (6 IU) in ages 0-6 months, males = 5 mg (7.5 IU) females = 5 mg (7.5 IU) in ages 7-12 months, males = 6 mg (9 IU) females = 6 mg (9 IU) in ages 1-3 years, males = 7 mg (10.4 IU) females = 7 mg (10.4 IU) in ages 4-8 years, males = 11 mg (16.4 IU) females = 11 mg (16.4 IU) in ages 9-13 years, males = 15 mg (22.4 IU) females = 15 mg (22.4 IU) pregnancy = 15 mg (22.4 IU) lactation = 19 mg (28.4 IU) in ages 14+ years [5]. Most individuals obtain adequate vitamin E intake from their diets; genuine vitamin E deficiency is considered to be rare.

Nevertheless, vitamin E is known to be a fat-soluble antioxidant that has the capability to neutralize endogenous free radicals. This biologic action of vitamin E consequently continues to generate ongoing interest and study in whether or not its antioxidant abilities may be used to help assist in preventing or treating a number of different conditions like cardiovascular disease, ocular conditions, diabetes, cancer and more. At the moment however, there exists a lack of formal data and evidence to support any such additional indications for vitamin E use.

Synonyms
  • DL-alpha tocopherol acetate
  • DL-alpha tocopheryl acetate
  • Tocopherol acetate
  • Tocopherol acetate, unspecified
  • Tocopheryl acetate
  • Vitamin E (alpha tocopherol acetate)
  • Vitamin E acetate
  • Vitamin E acetate, unspecified form
Categories
UNII
9E8X80D2L0
CAS number
7695-91-2
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

The primary health-related use for which alpha-tocopherol acetate is formally indicated is as a dietary supplement for patients who demonstrate a genuine vitamin E deficiency. At the same time, vitamin E deficiency is generally quite rare but may occur in premature babies of very low birth weight (< 1500 grams), individuals with fat-malabsorption disorders (as fat is required for the digestive tract to absorb vitamin E), or individuals with abetalipoproteinemia - a rare, inherited disorder that causes poor absorption of dietary fat - who require extremely large doses of supplemental vitamin E daily (around 100 mg/kg or 5-10 g/day) [5]. In all such cases, alpha-tocopherol is largely the preferred form of vitamin E to be administered.

Elsewhere, vitamin E's chemical profile as a fat-soluble antioxidant that is capable of neutralizing free radicals in the body continues to generate ongoing interest and study regarding how and whether or not the vitamin can help prevent or delay various chronic diseases associated with free radicals or other potential biological effects that vitamin E possesses like cardiovascular diseases, diabetes, ocular conditions, immune illnesses, cancer, and more [4]. None of these ongoing studies have yet to elucidate any formally significant evidence, however [4].

Structured Indications
Not Available
Pharmacodynamics

Of the eight separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability [6]. This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower [5].

Furthermore, the term alpha-tocopherol generally refers to a group of eight possible stereoisomers which is often called all-rac-tocopherol for being a racemic mixture of all eight stereoisomers [4, 6]. Of the eight stereoisomers, the RRR-alpha-tocopherol - or sometimes referred to as the d-alpha-tocopherol - stereoisomer is the naturally occurring form of alpha-tocopherol that is perhaps best recognized by the alpha-TTP [4, 6] and has been reported to demonstrate approximately twice the systemic availability of all-rac-tocopherol [6].

As a result, often times (but certainly not always) the discussion of vitamin E - at least within the context of using the vitamin for health-related indications - is generally in reference to the use of RRR- or d-alpha-tocopherol.

Mechanism of action

Vitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron [5]. These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) [5]. In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases [5]. Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun [5]. It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure [5].

Specifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions [4]. The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins [4]. Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids [4]. Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical [4]. This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids [4].

In addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E [4]. For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes [4]. In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity [4].

In addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium [4].

Vitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 [4]. The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans [4].

Furthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions [4]. The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets [4]. Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production [4].

Given these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis [4].

Similarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications [4]. In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA [4]. Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use [4]. Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action [4].

There have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals [4].

As of this time however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality) [1] on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.

TargetActionsOrganism
AFree radicals
binder
Human
Absorption

When vitamin E is ingested, intestinal absorption plays a principal role in limiting its bioavailability [2]. It is known that vitamin E is a fat-soluble vitamin that follows the intestinal absorption, hepatic metabolism, and cellular uptake processes of other lipophilic molecules and lipids [2]. The intestinal absorption of vitamin E consequently requires the presence of lipid-rich foods [2].

In particular, stable alpha-tocopherol acetate undergoes hydrolysis by bile acid-dependant lipase in the pancreas or by an intestinal mucosal esterase [2]. Subsequent absorption in the duodenum occurs by way of transfer from emulsion fat globules to water-soluble multi- and unilamellar vesicles and mixed micelles made up of phospholipids and bile acids [2]. As the uptake of vitamin E into enterocytes is less efficient compared to other types of lipids, this could potentially explain the relatively low bioavailability of vitamin E [2]. Alpha-tocopherol acetate itself is embedded in matrices where its hydrolysis and its uptake by intestinal cells are markedly less efficient than in mixed micelles [2]. Subsequently, the intestinal cellular uptake of vitamin E from mixed micelles follows in principle two different pathways across enterocytes: (a) via passive diffusion, and (b) via receptor-mediated transport with various cellular transports like scavenger receptor class B type 1, Niemann-Pick C1-like protein, ATP-binding cassette (ABC) transporters ABCG5/ABCG8, or ABCA1, among others [2].

Vitamin E absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion [4]. Defects at any step can lead to impaired absorption. [4]. Chylomicron secretion is required for vitamin E absorption and is a particularly important factor for efficient absorption. All of the various vitamin E forms show similar apparent efficiencies of intestinal absorption and subsequent secretion in chylomicrons [4]. During chylomicron catabolism, some vitamin E is distributed to all the circulating lipoproteins [4].

Chylomicron remnants, containing newly absorbed vitamin E, are then taken up by the liver [4]. Vitamin E is secreted from the liver in very low density lipoproteins (VLDLs). Plasma vitamin E concentrations depend upon the secretion of vitamin E from the liver, and only one form of vitamin E, alpha-tocopherol, is ever preferentially resecreted by the liver [4]. The liver is consequently responsible for discriminating between tocopherols and the preferential plasma enrichment with alpha-tocopherol [4]. In the liver, the alpha-tocopherol transfer protein (alpha-TTP) likely is in charge of the discriminatory function, where RRR- or d-alpha-tocopherol possesses the greatest affinity for alpha-TTP [4].

It is nevertheless believed that only a small amount of administered vitamin E is actually absorbed. In two individuals with gastric carcinoma and lymphatic leukemia, the respective fractional absorption in the lymphatics was only 21 and 29 percent of label from meals containing alpha-tocopherol and alpha-tocopheryl acetate, respectively [4].

Additionally, after feeding three separate single doses of 125 mg, 250 mg, and 500 mg to a group of healthy males, the observed plasma peak concentrations (ng/mL) were 1822 +/- 48.24, 1931.00 +/- 92.54, and 2188 +/- 147.61, respectively [7].

Volume of distribution

When three particular doses alpha-tocopherol were administered to healthy male subjects, the apparent volumes of distribution (ml) observed were: (a) at a single administered dose of 125 mg, the Vd/f was 0.070 +/- 0.002, (b) at dose 250. mg, the Vd/f was 0.127 +/- 0.004, and (c) at dose 500 mg, the Vd/f was 0.232 +/- 0.010 [7].

Protein binding

Data regarding the protein binding of alpha-tocopherol is not readily accessible at the moment. In fact, the existence of alpha-tocopherol binding proteins in tissues other than the liver is involved in ongoing investigations [4].

Metabolism

Primary hepatic metabolism of alpha-tocopherol begins in the endoplasmic reticulum with CYP4F2/CYP3A4 dependent ω-hydroxylation of the aliphatic side-chain, which forms the 13’-hydroxychromanol (13’-OH) metabolite [2]. Next, peroxisome ω-oxidation results in 13’-carboxychromanol (13’-COOH) [2]. Following these two steps are five consecutive β-oxidation reactions which serve to shorten the alpha-tocopherol metabolite side-chains [2]. The first of these β-oxidations occurs still in the peroxisome environment, generating carboxydimethyldecylhydroxychromanol (CDMDHC, 11’-COOH) [2]. Then, in the mitochondrion, the second β-oxidation step forms the carboxymethyloctylhydroxychromanol (CDMOHC, 9’-COOH) metabolite [2]. Since both CDMDHC and CDMOHC possess a side-chain length of between 13 to 9 carbon units, they are considered long-chain metabolites. The hydrophobicity of these long-chain metabolites means they are not excreted in the urine but have been found in human microsomes, serum, and feces [2]. The next two β-oxidation reactions, still within the mitochondrion environment, produce two intermediate chain metabolites: carboxymethylhexylhydroxychromanol (CDMHHC, 7’-COOH), followed by carboxymethylbutylhydroxychromanol (CMBHC, 5’-COOH) [2]. Both of these intermediate chain metabolites are found in human plasma, feces, and urine [2]. Finally, the last mitochrondrion β-oxidation generates the catabolic end product of alpha-tocopherol metabolism: carboxyethyl-hydroxychromans (CEHC, 3'-COOH), which is considered a short-chain metabolite [2]. CEHC has been observed in human plasma, serum, urine, and feces [2].

Route of elimination

The major route of excretion of ingested vitamin E is fecal elimination because of its relatively low intestinal absorption [4]. Excess alpha-tocopherol, as well as forms of vitamin E not preferentially used, are probably excreted unchanged in bile [4].

Half life

The apparent half-life of RRR- or d-alpha-tocopherol in normal subjects is approximately 48 hours [4].

Clearance

When three specific doses of 125 mg, 250 mg, and 500 mg of alpha-tocopherol were administered as single doses to a group of healthy males, the resultant times of clearance observed, respectively, were: 0.017 +/- 0.015 l/h, 0.011 +/- 0.001 l/h, and 0.019 +/- 0.001 l/h [7].

Toxicity

Tocopherols are considered as non-toxic but if very high doses (approximately >2 g/kg/day) are administered, there are reports of hemorrhagic activity [3]. Reproductive and developmental toxicity tests are negative [3]. These negative results were also observed in the analysis of mutagenicity and carcinogenicity [3]. The majority of these tests were animal feeding studies [3].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
Acetyl sulfisoxazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AmiodaroneThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Amiodarone.Approved, Investigational
ApalutamideThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of alpha-Tocopherol acetate can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Clemastine.Approved, Investigational
ClotrimazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with alpha-Tocopherol acetate.Approved, Investigational
CrizotinibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarunavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Diltiazem.Approved, Investigational
DoxycyclineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
FluconazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Fluconazole.Approved, Investigational
FluvoxamineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of alpha-Tocopherol acetate can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Fusidic Acid.Approved, Investigational
IdelalisibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Indinavir.Approved
IsavuconazoleThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of alpha-Tocopherol acetate can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of alpha-Tocopherol acetate can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Palbociclib.Approved, Investigational
PentobarbitalThe metabolism of alpha-Tocopherol acetate can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of alpha-Tocopherol acetate can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of alpha-Tocopherol acetate can be increased when combined with Phenytoin.Approved, Vet Approved
PitolisantThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of alpha-Tocopherol acetate can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of alpha-Tocopherol acetate can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of alpha-Tocopherol acetate can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of alpha-Tocopherol acetate can be increased when combined with Rifapentine.Approved, Investigational
RucaparibThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of alpha-Tocopherol acetate can be decreased when used in combination with Sarilumab.Approved, Investigational
SildenafilThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of alpha-Tocopherol acetate can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Tocilizumab.Approved
VemurafenibThe serum concentration of alpha-Tocopherol acetate can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of alpha-Tocopherol acetate can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. [PubMed:15537682]
  2. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
  3. Zondlo Fiume M: Final report on the safety assessment of Tocopherol, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, Potassium Ascorbyl Tocopheryl Phosphate, and Tocophersolan. Int J Toxicol. 2002;21 Suppl 3:51-116. doi: 10.1080/10915810290169819. [PubMed:12537931]
  4. Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press (US). [ISBN:0309069491]
  5. National Institute for Health [Link]
  6. Cosmetic Ingredient Review: Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics [Link]
  7. Journal of Clinical & Experimental Cardiology: Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects [Link]
External Links
Not Available
MSDS
Download (47.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)10 degrees CelciusMSDS
boiling point (°C)>343 degrees CelciusMSDS
water solubilityInsoluble in cold water and hot waterNot Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. Free radicals
Kind
Group
Organism
Human
Pharmacological action
Yes
Actions
Binder
References
  1. Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press (US). [ISBN:0309069491]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Very-low-density lipoprotein particle receptor activity
Specific Function
Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine p...
Gene Name
VLDLR
Uniprot ID
P98155
Uniprot Name
Very low-density lipoprotein receptor
Molecular Weight
96097.45 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
2. High density lipoprotein
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Binder
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Virus receptor activity
Specific Function
Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clat...
Gene Name
LDLR
Uniprot ID
P01130
Uniprot Name
Low-density lipoprotein receptor
Molecular Weight
95375.105 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin e binding
Specific Function
Binds alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells (PubMed:7887897). Binds both phosphatidylinol 3,4-bisphosphate and phosphatidyl...
Gene Name
TTPA
Uniprot ID
P49638
Uniprot Name
Alpha-tocopherol transfer protein
Molecular Weight
31749.305 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.
Gene Name
SEC14L4
Uniprot ID
Q9UDX3
Uniprot Name
SEC14-like protein 4
Molecular Weight
46643.385 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin e binding
Specific Function
Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinit...
Gene Name
SEC14L2
Uniprot ID
O76054
Uniprot Name
SEC14-like protein 2
Molecular Weight
46144.9 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.
Gene Name
SEC14L3
Uniprot ID
Q9UDX4
Uniprot Name
SEC14-like protein 3
Molecular Weight
46047.835 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Transporter
General Function
Very-low-density lipoprotein particle receptor activity
Specific Function
Macrophage receptor that binds to the apolipoprotein B48 (APOB) of dietary triglyceride (TG)-rich lipoproteins (TRL) or to a like domain of APOB in hypertriglyceridemic very low density lipoprotein...
Gene Name
APOBR
Uniprot ID
Q0VD83
Uniprot Name
Apolipoprotein B receptor
Molecular Weight
114873.425 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Transporter
General Function
Virus receptor activity
Specific Function
Receptor for different ligands such as phospholipids, cholesterol ester, lipoproteins, phosphatidylserine and apoptotic cells. Probable receptor for HDL, located in particular region of the plasma ...
Gene Name
SCARB1
Uniprot ID
Q8WTV0
Uniprot Name
Scavenger receptor class B member 1
Molecular Weight
60877.385 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Transporter
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [PubMed:26981194]

Drug created on March 25, 2018 14:54 / Updated on May 02, 2018 00:41