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Vitamin E

Terms in this set (21)

What forms of Vitamin E are in the diet?
Vitamin E is a family of 8 antoxidant molecules (4 tocopherols and 4 tocotrienols)

What germ, almonds, spinach are especially rich in alpha-tocopherol.

Soy and corn oils especially rich in gamma-tocopherol.

Alpha-tocopherol is the only form of vitamin E actively maintained in the human body; found in the largest quantities in blood and tissues.
How is Vitamin E absorbed by the enterocyte?
Vitamin E is absorbed primarily in the jejunum by passive diffusion.

NPC1L1 may also play a role in absorption.

Bile salts are required for emulsification, solubilization, and micelle formation.

Rate of absorption: highly variable (10-80%).
How does Vitamin E move and circulate in systemic circulation (carriers)?
After being absorbed, vitamin E is packaged in chylomicrons.

LPL carries fatty acids and vitamin E to tissues.

HDL carries fitamin E to tissues.

Chylomicrons carry vitamin E to the liver for liver uptake.

Alpha-tocopherol transport protein (alpha-TTP)
Pathways for the preferential delivery of alpha-tocopherol to peripheral tissues
Vitamin E taken up by the liver with chylomicron remnants

Some vitamin E is excreted from the liver with bile

Preferential selection of 2R-alpha-tocopherol in VLDL

VLDL undergoes lipolysis to LDL and HDL, which both end up with alpha-tocopherol

Tissue uptake of alpha-tocopherol coccurs
Alpha-tocopherol transport protein
Cytosolic 32kDa protein; facilitates secretion of alpha-tocopherol from liver into the plasma for distribution to tissues.

Tissue expression: high in liver; lower levels in brain, kidney, lung, spleen

Only natural alpha-tocopherol (RRR-alpha-tocopherol) and 2R-alpha-tocopherol in synthetic all-rac-alpha-tocopherol are maintained in plasma due to the selectivity of alpha-TTP.
Role of alpha-TTP in vitamin E metabolism and distribution
Alpha-TTP helps release vitamin E into VLDL, HDL, and carry to target tissues

Mutated or deleted liver's alpha-TTP: ataxia and vitamin E deficiency (AVED)
How and where is vitamin E stored?
More than 90% of the human body pool of alpha-tocopherol is located in the adipose tissue, with more than 90% of adipose tissue alpha-tocopherol in fat droplets
What are the target tissues of vitamin E?
More than 90% in adipose tissue.

Vitamin E is used in virtually all tissues as a fat-soluble antioxidant.
What are the functions of Vitamin E in target tissues? (5 major categories)
1) Antioxidant
2) Gene expression
3) Cell signaling
4) Relationship with vitamin C
5) Plays roles in eye and neurological functions; inhibition of platelet coagulation; protection of lipids; enzymatic activity regulator for PKC; peroxyl radical scavenger
Vitamin E as Antioxidant
Vitamin E provides a hydrogen for the reduction of lipid carbon-centered radicals.

Quenching of free radical activity.
Vitamin E and Vitamin C Relationship
As a result of Vitamin E's free radical quenching activity, it itself becomes radicalized (alpha-tocopherol radical).

The ascorbate monoanion from the vitamin C cycle regenerates alpha-tocopherol from the alpha-tocopherol radical.
How is Vitamin E metabolized and excreted?
Vitamin E first undergoes a series of oxidations.

After oxidations, it encounters alpha-CEHC (2-carboxyethyl-6-hydroxychroman), which leads to vitamin E being conjugated with glucuronic acid and excretion in urine.
How is Vitamin E homeostasis assessed?
Mainly determined by blood analyses: plasma levels reflect dietary intake under deficiency and toxicity situations

Normal: 5-20 ug/mL in adults
Deficiency < 5 ug/mL
Toxicity: > 20 ug/mL

Plasma gamma-tocopherol levels generally 1/10 of alpha-tocopherol levels
"At Risk" populations for deficiency
Primary vitamin E deficiency is rare; it occurs only in premature children, genetic alterations, malabsorption, and parenteral nutrition.

1) Genetic abnormalities:
- tocopherol transfer protein (AVED)
- Apolipoprotein B (homozygous hypobetalipoprotenemia)
- Microsomal triglyceride transfer protein (abetalipoproteinemia)

2) Fat malabsorption syndromes including chronic cholestasis; cystic fibrosis; pancreatic insufficiency; short bowel syndromes; and chronic steatorrhea

3) TPN
Vitamin E Toxicity
Generally safe even at high levels; hypervitaminosis of vitamin E along with other blood thinners may exacerbate anti-coagulation / bleeding problems.
Vitamin E Deficiency
Results in nerve problems due to poor conduction of electrical impulses due to changes in nerve membrane structure and function.
Vitamin E and Health Benefits
Might help prevent formation of blood clots

Protect cell constituents from damaging free radicals

Might block formation of carcinogenic nitrosamines; enhance immune function
Vitamin E and CVD
Heart Outcomes Prevention evaluation found no significant effects of vitamin E.
Vitamin E and Cancer Risk
Statistically non-significant increased risk of prostate cancer with vitamin E treatment

Equivocal evidence of decreased colon cancer risk

No benefit in breast cancer

Possible evidence of reduced mortality from bladder cancer
Vitamin E and All Mortality
Meta-analysis shows high-dosage vitamin E supplementation may increase all-cause mortality
Vitamin E and Alzheimer's Disease
Evidence suggests that alpha-tocopherol is beneficial in mild to moderate Alzheimer's by slowing functional decline and decreasing caregiver burden
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