1. Vitamin E
Slides prepared by Dr. Ashok Moses
for Franco-Indian Pharmaceuticals
Ltd.

2. Vitamin E
• Vitamin E refers to a group of eight fat-soluble
compounds that include both tocopherols and
tocotrienols.[1] Of the many different forms of vitamin
E, γ-tocopherol is the most common in the North
American diet.[2] γ-Tocopherol can be found in corn
oil, soybean oil, margarine, and dressings.[3][4] In the
North American diet, α-tocopherol, the most
biologically active form of vitamin E, is the second-
most common form of vitamin E. This variant can be
found most abundantly in wheat germ oil, sunflower,
and safflower oils.[4][5] As a fat-soluble antioxidant, it
stops the production of reactive oxygen species formed
when fat undergoes oxidation.[6][7][8]

3. Functions
Vitamin E has many biological functions, the antioxidant
function being the most important and/or best known.[9]
Other functions include enzymatic activities, gene expression,
and neurological function(s). The most important function of
vitamin E has been suggested to be in cell signaling (and it
may not have a significant role in antioxidant
metabolism).[10][11]
• As an antioxidant, vitamin E acts as a peroxyl radical
scavenger, preventing the propagation of free radicals in
tissues, by reacting with them to form a tocopheryl radical,
which will then be reduced by a hydrogen donor (such as
vitamin C) and thus return to its reduced state.[12] As it is
fat-soluble, it is incorporated into cell membranes, which
protects them from oxidative damage.

4. Functions
• As an enzymatic activity regulator, for
instance, protein kinase C (PKC), which plays a
role in smooth muscle growth, can be
inhibited by α-tocopherol. α-Tocopherol has a
stimulatory effect on the dephosphorylation
enzyme, protein phosphatase 2A, which in
turn, cleaves phosphate groups from PKC,
leading to its deactivation, bringing the
smooth muscle growth to a halt.[13]

5. Functions
• Vitamin E also has an effect on gene expression.
Macrophages rich in cholesterol are found in the
atherogenetic tissue. Scavenger receptor CD36 is a
class B scavenger receptor found to be up-regulated by
oxidized low density lipoprotein (LDL) and binds it.[14]
Treatment with α-tocopherol was found to
downregulate the expression of the CD36 scavenger
receptor gene and the scavenger receptor class A (SR-
A)[14] and modulates expression of the connective
tissue growth factor (CTGF).[15][16] The CTGF gene,
when expressed, is responsible for the repair of
wounds and regeneration of the extracellular tissue
lost or damaged during atherosclerosis.[16]

6. Functions
• Vitamin E also plays a role in neurological functions,[17]
and inhibition of platelet aggregation.[18][19][20]
• Vitamin E also protects lipids and prevents the oxidation of
polyunsaturated fatty acids.[21]
So far, most human supplementation studies about vitamin E
have used only α-tocopherol. This can affect levels of other
forms of vitamin E, e.g. reducing serum γ- and δ-tocopherol
concentrations. Moreover, a 2007 clinical study involving α-
tocopherol concluded supplementation did not reduce the
risk of major cardiovascular events in middle-aged and older
men.[22]

7. Deficiency
Vitamin E deficiency can cause:
• Spino-cerebellar ataxia[23]
• Myopathies[4]
• Peripheral neuropathy[6][24][25]
• Ataxia[6][24][25]
• Skeletal myopathy[6][24][25]
• Retinopathy[6][24][25]
• Impairment of the immune response[6][24][25]
• Red blood cell destruction[21]

8. Dietary sources
mg/(100 g) Some foods with vitamin E content[6]
low/high
• 150 Wheat germ oil
• 41 Sunflower oil
• 34 Safflower oil
• 15/26 Nuts and nut oils, such as almonds and hazelnuts[note 2]
• 15 Palm oil[34]
• 1.5/3.4 High-value green, leafy vegetables: spinach, turnip, beet greens, collard greens,
and dandelion greens[note 3]
• 2.1 Avocados
• 1.1/1.5 Asparagus[note 4]
• 1.5 Kiwifruit (green)
• 0.78/1.5 Broccoli[note 5]
• 0.8/1 Pumpkin[note 6]
• 0.26/0.94 Sweet potato[note 7][note 8]
• 0.9 Mangoes
• 0.54/0.56 Tomatoes[note 9]
• 0.36/0.44 Rockfish[note 10]
• 0.3 Papayas
• 0.13/0.22 Low-value green, leafy vegetables: lettuce[note 11]

9. Recommended daily intake
The Food and Nutrition Board at the Institute of Medicine (IOM) of the US National Academy of
Sciences reported the following dietary reference intakes for vitamin E:[6][35]
mg/day Age
Infants
• 4 0 to 6 months
• 5 7 to 12 months
Children
• 6 1 to 3 years
• 7 4 to 8 years
• 11 9 to 13 years
Adolescents and adults
• 15 14 and older
One IU of vitamin E is defined as equivalent to either: 0.67 mg of the natural form, RRR-α-
tocopherol, also known as d-α-tocopherol; or 0.45 mg of the synthetic form, all-rac-α-
tocopherol, also known as dl-α-tocopherol.[6]

10. History
• The first use for vitamin E as a therapeutic agent was
conducted in 1938 by Widenbauer, who used wheat
germ oil supplement on 17 premature newborn infants
suffering from growth failure. Eleven of the original 17
patients recovered and were able to resume normal
growth rates.[9]
• In 1945, Drs. Evan V. Shute and Wilfred E. Shute,
siblings from Ontario, Canada, published the first
monograph arguing that megadoses of vitamin E can
slow down and even reverse the development of
atherosclerosis.[36] Peer-reviewed publications soon
followed.[37][38]

11. History
• The same research team also demonstrated, in
1946, that α-tocopherol improved impaired
capillary permeability and low platelet counts in
experimental and clinical thrombocytopenic
purpura.[39]
• Later, in 1948, while conducting experiments on
alloxan effects on rats, Gyorge and Rose noted
rats receiving tocopherol supplements suffered
from less hemolysis than those that did not
receive tocopherol.[40]

12. History
• In 1949, Gerloczy administered all-rac-α-
tocopheryl acetate to prevent and cure
edema.[41][42] Methods of administration used
were both oral, that showed positive response,
and intramuscular, which did not show a
response.[9] This early investigative work on the
benefits of vitamin E supplementation was the
gateway to curing the vitamin E deficiency-caused
hemolytic anemia described during the 1960s.
Since then, supplementation of infant formulas
with vitamin E has eradicated this vitamin’s
deficiency as a cause for hemolytic anemia.[9]

13. Forms
The eight forms of vitamin E are divided into
two groups; four are tocopherols and four are
tocotrienols. They are identified by prefixes
alpha- (α-), beta- (β-), gamma- (γ-), and delta-
(δ-). Natural tocopherols occur in the RRR-
configuration only. The synthetic form contains
eight different stereoisomers and is called 'all-
rac'-α-tocopherol.[43]

14. Forms
• α-Tocopherol [edit]
α-Tocopherol is an important lipid-soluble antioxidant. It performs its
functions as antioxidant in the glutathione peroxidase pathway,[44]and it
protects cell membranes from oxidation by reacting with lipid radicals
produced in the lipid peroxidation chain reaction.[23][7] This would remove
the free radical intermediates and prevent the oxidation reaction from
continuing. The oxidized α-tocopheroxyl radicals produced in this
process may be recycled back to the active reduced form through
reduction by other antioxidants, such as ascorbate,retinol or ubiquinol
However, the importance of the antioxidant properties of this molecule at
the concentrations present in the body are not clear and the reason
vitamin E is required in the diet is possibly unrelated to its ability to act
as an antioxidant.[46] Other forms of vitamin E have their own unique
properties; for example, γ-tocopherol is a nucleophile that can react
with electrophilic mutagens.[47]

15. Forms
• Tocotrienols
Compared with tocopherols, tocotrienols are sparsely studied.[48][49][50] Less
than 1% of PubMed papers on vitamin E relate to tocotrienols.[51] The current
research direction is starting to give more prominence to the tocotrienols, the
lesser known but more potent antioxidants in the vitamin E family. Some studies
have suggested that tocotrienols have specialized roles in
protecting neurons from damage[51] and cholesterol reduction[52] by inhibiting
the activity of HMG-CoA reductase; δ-tocotrienol blocks processing of sterol
regulatory element‐binding proteins (SREBPs).
Oral consumption of tocotrienols is also thought to protect against stroke-
associated brain damage in vivo.[53] Until further research has been carried out
on the other forms of vitamin E, conclusions relating to the other forms of
vitamin E, based on trials studying only the efficacy of α-tocopherol, may be
premature.[54]