Vitamin E

E Vitamin encompasses 8 compounds (VITAMERS)

• Each contain:
• The Head: A phenolic functional groups on a chromanol/chromane ring
• The Tail: an attached phytyl side chain
• 2 classes which contain 4 VITAMERS each, differ in # and location of methyl groups on the chromanol ring:
• TOCOPHEROLS - saturated side chains with 16-carbons
• a, B, y, o
• Only a-Tocapherol has biological activity and can meet body's need for the vitamin and cannot interconnect with other vitamers
• TOCOTRIENOLS (TIENOLS) - unsaturated side chains with 16-carbons
• a, B, y, o

Tocopherol: toco means "childbirth", pherol means "to bring forth", discovery by H Evans and K Bishop 1922

SOURCES:

• Plant (see below)
• Animal - fatty tissues, not as good a source as plant
• Supplements
• 30 IU daily RDA, supplements range from 100-800 IU
• Synthetic all-racemic
• 2/3rd adult not meeting RDA, esp if low fat diet
• Tocotrienols - found in Palm oil
• Creams - vit E  acetate, no proof heals scarring
• Food preparation:
• Oxidizes easily
• Heating wheat germ removes vit E
• Toasting nuts removes vit ED

DIGESTION and ABSORPTION:

Tocopherols are found free is food, the tocotrienols are esterified and must be hydrolyzed before absorption. Synthetic tocopherols are often esterified (tocopherol acetate).

Pancreatic esterase and duodenal mucosal esterase (carboxyl ester hydrocylase) function in the lumen or at brush border membrane of enterocytes to hydrolyze esters to be absorbed.

Absorption occurs in the jejunum by passive diffusion. Bile salts are required for emulsion, solubilzation, and micelle formation - allowing for passive diffusion.

Simultaneous digeston and absorption of dietary lipids improves vitamin E absorption which is 20-70%. Higher intake appears to reduce its absorption. 

TRANSPORT, METABOLISM, STORAGE:

In the enterocyte, absorbed vit E is incorporated into chylomicrons for transport through lymph and then into circulation. 

Hepatic uptake occurs with delivery via chylomicrons. The liver metabolizes all vit E but only TRAFFIKS RRR a-tocopherol via lipoproteins.

Vitamin E is transferred by a-TOCOPHEROL TRASNSFER PROTEIN (aTTP), which is made in the liver, to VLDL and released into blood. Deficiency of vit E can occur with liver conditions (NASH,) or aTTP deficiency. 

Vit E is transferred among HDL, LDL and VLDL, and the exchange is mediated by PHOSPHOLIPID TRANSFER PROTEIN. Bound to protein the vit E level is 5-20 mg/L. LDL containts 5-0 a-tocopherol molecules/LDL. The half life of RRR form is 48 hours.

Vit E uptake into cells occurs in association with lipoproteins:

• Receptor mediated uptake of LDL
• LIPOPROTEIN LIPASE MEDIATED HYDROLYSIS of chylomicrons and VLDL
• HDL mediated nutrient deliver
• A phospholipid transfer protein may facilitate vitamine E transfer from liporprotein to cell membranes.

Within the cell cytosol or nucleus, vitamin E bind to specific TOCOPHEROL BINDING PROTEINS for intracellular transport. ATP-binding cassette (ABC) A1 is thought to be involved in cellular trafficking and efflux from cells.

Vit E is incorporated into the phopholipid bilayer of membranes including plasma, mitochondrial, and microsomal membranes.

No single storage organ for vit E although over 90% concentrated in unesterfied form in fat droplets in adipose tissue where re-release to circulation is slow. 

MECHANISM OF ACTION:

(1) ANTIOXIDANT - primary function; protects membrane from destruction by preventing oxidation (peroxidation) of unsaturated fatty acids in the phospholipids of the membranes. 

• Vitamin E and heart disease 
• Oxidation of LDLs > atherosclerosis
• Diminish platelet aggregation and clotting
• Cancer
• Free radical induced damage
• May worsen prostate cancer
• Eye Health
• Macular degneration
• Cataracts
• Other:
• Metabolic stress related lipid peroxidation
• iron toxicity
• diabetes
• NASH
• Maintaining cell structure, increases cell uptake of glucose
• Bone health and reduced fracture risk
• Neurodegnerative consitions like AD PD

(2) Cell Signaling, gene expression

• Inhibition of protein kinase C (a serine/tyrosine kinase) that functions in transduction of signals from G protein-couple tyrosine kinase receptors to the nucleus by hydrolysis of phosphlilpids.
• Steroidogenesis, lipid uptake, cell cycle, inflammation, cell adhesion, blood coagulation.

INTERACTIONS:

Selenium:

• antioxidant functions of vit E tied to selenium-dependent glutacthione peroxidase (coverts lipid peroxides into lipid alcohols)
• actions of selenium and vit E complementary

Vitamin C

• vit C can regenerate vit E following its oxidation.

Polyunsaturated fats

B=Carotene

• Vit E inhibits B-carotene absorption in intestines

Vitamin K

• Vit E interferes with absorption and metabolism of vit K including conversion of phylloquinone to menaquinone
• Increased risk of bleeding with vit E due to interfering with vit K role.

EXCRETION

Hepatic metabolism begins with omega-hydroxylation reaction requiring cytochrome P450 to form hydroxychromanol.

A series of reactions analagous to B-oxidation of fatty acids follows to truncate vit E phytyl side chain.

End products are group of carboxyethyl hydroxychromans (CHEC) which are cojugated to glucuronic acid or sulfate.

Urinary excretion occurs.

RDA

1IU = 0.67 mg (natural sources)

1IU = 0.45 mg (synthetic)

15 mg (22 IU of RRR or 33 IU of synthetic vit E daily

Lactation increases to 19 mg 28 IU.

Higher requirements may exist in:

• oxidative stress
• inflammatory conditions 
• smokers
• metabolic syndrome

DEFICIENCY

Rare

Populations at risk:

• Premature infants (RBC hemolysis)
• Exhibit impaired fat utilizaiton due to prematurity
• Fat malabsorption disorders:
• Cystic fibrosis (pancreatic lipase deficiency)
• Hepatobiliary systems disorders like chronic cholestasis with decreased bile production
• Genetic defects:
• in lipoprotein or tocopherol transfer proteins
• Abetalipoproteinemia (lack of microsomal transfer protein needed to assemble or secrete lipoproteins containing apo B
• aTTP defect cannot release vit E into blood

TOXICITY

Least toxic of fat soluble vitamins

Increased tendancy for bleeding/impaired blood coagulation due to antiplatelet effects

Tolerable UL = 1,000 mg or 1500 IU daily. 

ASSESSMENT of STATUS

Blood analysis

<5 mg/L to 20 mg/L

Erythrocyte Hemolysis Test