Vitamin E and Selenium

Nov 6, 2013

Forms of vitamin E: alpha-tocopherol is the most active

1. Tremendous hype as “wonder vitamin” – “prevents aging, heart disease, cancer, improves sex life, promotes wound healing”.

 Virtually none of this has been rigorously substantiated, but the vitamin pushers work hard to keep the myth alive. (Dr. Handelman’s judgement!).

 2. Only defined role: protects polyunsaturated fatty acids (PUFA) from

peroxidation. Since the CNS, and the membranes of the mitochondria, and are very rich in PUFA, vitamin E deficiency first attacks the central nervous system and muscles.

 All forms of vitamin E work pretty well, but only the a-tocopherol form istenaciously retained by the body (see below).

3. Deficiency in humans takes many years to develop, since we store several grams in our fat tissues. First tissue to be damaged is the retina, since the retina is very rich in fatty acids with 6 double bonds.  4. Long-term deficiency leads to spinal cord degeneration and muscle atrophy.  5. If your diet is high in PUFA, such as from fish, you more vitamin E

in your diet. However, since vitamin E is plentiful in whole grains, vegetable oils, and green vegetables, even people who eat a lot of seafood get enough for health, and they don’t need supplemental

vitamin E.

6. Since vitamin E is NOT water-soluble, it is transported in the bloodstream inthe lipoprotein particles (LDL and HDL). The diagram in the handout shows whyonly form, RRR-alpha-tocopherol, is conserved in the tissues.

 PEOPLE WHO LACK THIS BINDING PROTEIN require high daily doses of a-tocopherol to avoid being deficient.

  7. Since 1990, there have been 4 large trials of vitamin E supplements to prevent

heart disease – none has been effective, but other interventions (aspirin, ACEinhibitors, drugs to lower cholesterol) have been quite effective!

INITIAL FORMATION OF A PEROXYL RADICALFROM UNSATURATED FATTY ACID

IF THESE EVENTS OCCUR IN THE MEMBRANE, THERE CAN BE SUBSTANTIAL DISTURBANCE TO THE STRUCTURE OF THE BILAYER, AS THE DAMAGED FATTY ACID “STICKS OUT”.

THIS TRIGLYCERIDE HAS

TWO SATURATED FATTY ACIDS, AND

ONE POLYUNSATURATED FATTY ACID

PALMITIC ACID: SATURATED FAT

OLEIC ACID (1 DOUBLE BOND):MONOUNSATURATED FAT

These fatty acids do not peroxidize.Which foods contain a lot of these fatty acids?

THESE ARE TWO IMPORTANT POLYUNSATURATEDTHESE ARE TWO IMPORTANT POLYUNSATURATEDFATTY ACIDS. THEY HAVE A VERY POWERFULFATTY ACIDS. THEY HAVE A VERY POWERFUL

IMPACT ON NUTRITION.IMPACT ON NUTRITION.

BOTH OF THESE FATTY ACIDS PEROXIDIZE

THESE ARE TWO IMPORTANT POLYUNSATURATEDTHESE ARE TWO IMPORTANT POLYUNSATURATEDFATTY ACIDS. THEY HAVE A VERY POWERFULFATTY ACIDS. THEY HAVE A VERY POWERFUL

IMPACT ON NUTRITION.IMPACT ON NUTRITION.

THESE FATTY ACIDS ARE OBTAINED FROM SEAFOOD, IN ADDITION TO BEING MADE IN YOUR TISSUES. THEY ARE

MAJOR COMPONENTS OF THE CNS AND RETINA.

THEY PEROXIDIZE VERY FAST,

WHICH IS WHY FISH DOES NOT KEEP WELL.

THE VERY HIGH ABUNDANCE OF EPAAND DHA IN THE BRAIN AND RETINA

EXPLAINS:

WHY THE MAJOR LESIONSOF VITAMIN E DEFICIENCY IN HUMANS

OCCUR IN THE CNS.

INITIAL FORMATION OF A PEROXYL RADICALFROM UNSATURATED FATTY ACID

THIS RADICALATTACKSANOTHER FATTYACID WITH MANYDOUBLE BONDS

Once an initial radical attack is made on a fatty acid –

The first fatty acid radical will attack ANOTHERunsaturated fatty acid.

Then another, and another.

The first radical attack can lead to the destructionof hundreds of polyunsaturated fatty acids.

VITAMIN E TO THE RESCUE!

CH3•

CH4

Tocopheroxy radical (harmless)

•+

Alpha-TocopherolMethylradical

(dangerous)

Methane

In this scenario, the methyl radical reacts directly with vitamin E, to form methane, and the harmless tocopheroxy radical.

MORE TYPICALLY, VITAMIN EREACTS WITH LIPID-OO• RADICALS

TOCOPHEROLDONATES HERETO CREATE THELIPID PEROXIDEPRODUCT

.

VITAMIN E CONVERTS THE VERY DANGEROUS

ROO• INTO THE LESS DANGEROUS ROOH

(lipid hydroperoxide).

IT IS NOW UP TO Glutathione peroxidase

TO REMOVE THE ROOH.

VITAMIN E AND GLUTATHIONE PEROXIDASE

WORK TOGETHER IN THE CELL.

Glutathione peroxidase

(abbreviated, “GSH-Px”

is a Selenium-Dependent ENZYME

that converts peroxides to alcohols.

The electrons for this reduction

come from glutathione (GSH).

+ GSH-Px (active enzyme)

H

Product is ~harmlessalcohol of fatty acid

+ GSH-Px (inactive enzyme)

GSH-Px (active)

GSH-Px (inactive) + 2 GSH

+ GSSG

GSSG + NADPH 2 GSH + NADP+

The enzyme is then reactivated by glutathione.

Glutathione reductase enzyme

Finally, all the GSSG is converted back to GSH

H

GSHGSH-disulfide

(or GSSG)

1) Fatty-acid-OOH + GSH-Px (active) Fatty-acid-OH +GSH-Px (inactive)

2) GSH-Px (inactive) + 2 GSH GSH-Px (active) + GSSH

3) GSSG + NADPH 2 GSH + NADP+

THE GLUTATHIONE PEROXIDASE PATHWAY.

The first step requires selenium.

CONSERVATION OF RRR-alpha-TOCOPHEROLBY THE HEPATIC BINDING PROTEIN

LIVER

DIET: Many forms of vitamin E

RRR-alpha-tocopherol other isomers of alpha-T gamma-tocopherol delta-tocopherol tocotrienols

Intestinal lumen

Lymph chylomicrons

Bloodstream

Chylomicron remnants, containingall different forms of vitamin E

RRR-a-tocopherol

Binding proteingrabs alpha-T

VLDL

Bloodstream(mostly, alpha-T)

LDL

Others forms ofvitamin E

BILE: Largelygamma-T

A-TOCOPHEROL IS RAPIDLY EXCRETEDIF THE BINDING PROTEIN IS DEFECTIVE

LIVER

DIET: Many forms of vitamin E

RRR-alpha-tocopherol other isomers of alpha-T gamma-tocopherol delta-tocopherol tocotrienols

Intestinal lumen

Lymph chylomicrons

Bloodstream

Chylomicron remnants, containingall different forms of vitamin E

RRR-a-tocopherol

Binding proteingrabs alpha-T

VLDL

Bloodstream(mostly, alpha-T)

LDL

Others forms ofvitamin E

BILE: alpha-Tand gamma-T