Vitamin E (alpha Tocopherol Acetate)

Uses

Vitamin E (alpha Tocopherol Acetate) is a form of vitamin E used to treat and prevent vitamin deficiencies.

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) . 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 . None of these ongoing studies have yet to elucidate any formally significant evidence, however .

Vitamin E (alpha Tocopherol Acetate) is also used to associated treatment for these conditions: Deficiency, Vitamin A, Vitamin Deficiency, Vitamin E Deficiency, Deficiency, Vitamin D, Nutritional supplementation

How Vitamin E (alpha Tocopherol Acetate) works

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 . These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) . In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases . 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 . 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 .

Specifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions . The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins . Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids . Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical . 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 .

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 . 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 . 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 .

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 .

Vitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 . 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 .

Furthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions . 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 . 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 .

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 .

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 . 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 . 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 . 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 .

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 .

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) on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.

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 . Reproductive and developmental toxicity tests are negative . These negative results were also observed in the analysis of mutagenicity and carcinogenicity . The majority of these tests were animal feeding studies .

Food Interaction

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 .

Elimination Route

When vitamin E is ingested, intestinal absorption plays a principal role in limiting its bioavailability . 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 . The intestinal absorption of vitamin E consequently requires the presence of lipid-rich foods .

In particular, stable alpha-tocopherol acetate undergoes hydrolysis by bile acid-dependant lipase in the pancreas or by an intestinal mucosal esterase . 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 . 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 . 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 . 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 .

Vitamin E absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion . Defects at any step can lead to impaired absorption. . 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 . During chylomicron catabolism, some vitamin E is distributed to all the circulating lipoproteins .

Chylomicron remnants, containing newly absorbed vitamin E, are then taken up by the liver . 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 . The liver is consequently responsible for discriminating between tocopherols and the preferential plasma enrichment with alpha-tocopherol . 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 .

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 .

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 .

Half Life

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

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 .

Elimination Route

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

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