ArticlePDF AvailableLiterature Review

The Role of Vitamin E in Human Health and Some Diseases


Abstract and Figures

Vitamin E is the major lipid-soluble component in the cell antioxidant defence system and is exclusively obtained from the diet. It has numerous important roles within the body because of its antioxidant activity. Oxidation has been linked to numerous possible conditions and diseases, including cancer, ageing, arthritis and cataracts; vitamin E has been shown to be effective against these. Platelet hyperaggregation, which can lead to atherosclerosis, may also be prevented by vitamin E; additionally, it also helps to reduce the production of prostaglandins such as thromboxane, which cause platelet clumping. The current literature review discusses the functions and roles of vitamin E in human health and some diseases as well as the consequences of vitamin E deficiency. The main focus of the review is on the tocopherol class of the vitamers.
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S Q U M J, M , V. , I. , . e-, E. TH A 
S ST A 
R R. ST O ; R R. TH O 
A ST O 
V E     
to a group of fat-soluble compounds first
discovered in 1922 by Evans and Bishop;
these compounds have distinct antioxidant activities
essential for health.1 Vitamin E is present in fat-
containing foods2 and, as the fat-soluble property of the
vitamin allows it to be stored within the fatty tissues of
animals and humans, it does not have to be consumed
every day. e vitamin E group (i.e. chroman-6-ols),
collectively termed tocochromanols (divided into
tocopherols and tocotrienols), includes all of the tocol
and tocotrienol derivatives which qualitatively exhibit
the biological activity of d-alpha-tocopherol.
ere are eight naturally occurring forms of
vitamin E; namely, the alpha, beta, gamma and delta
classes of tocopherol and tocotrienol, which are
synthesised by plants from homogentisic acid. Alpha-
and gamma-tocopherols are the two major forms of
the vitamin, with the relative proportions of these
depending on the source. e richest dietary sources
of vitamin E are edible vegetable oils as they contain
all the different homologues in varying proportions
[Table 1]. Among the tocopherols, the alpha- and
gamma-tocopherols are found in the serum and the
red blood cells, with alpha-tocopherol present in the
highest concentration.3 Beta- and delta-tocopherols
are found in the plasma in minute concentrations only.
e preferential distribution of alpha-tocopherol in
humans over the other forms of tocopherol stems from
the faster metabolism of the other forms and from
the alpha-tocopherol transfer protein (alpha-TTP). It
is due to the binding affinity of alpha-tocopherol with
alpha-TTP that most of the absorbed beta-, gamma-
and delta-tocopherols are secreted into the bile and
excreted in the faeces, while alpha-tocopherol is largely
excreted in the urine. e alpha-tocopherol form also
accumulates in the non-hepatic tissues, particularly
at sites where free radical production is greatest,
such as in the membranes of the mitochondria and
endoplasmic reticulum in the heart and lungs.
is review mainly focuses on the current
developments in vitamin E research in the context
Department of Biochemistry, ERA’S Lucknow Medical College India, Lucknow, India
*Corresponding Author e-mail:
: Vitamin E is the major lipid-soluble component in the cell antioxidant defence system and is
exclusively obtained from the diet. It has numerous important roles within the body because of its antioxidant
activity. Oxidation has been linked to numerous possible conditions and diseases, including cancer, ageing,
arthritis and cataracts; vitamin E has been shown to be effective against these. Platelet hyperaggregation, which
can lead to atherosclerosis, may also be prevented by vitamin E; additionally, it also helps to reduce the production
of prostaglandins such as thromboxane, which cause platelet clumping. e current literature review discusses
the functions and roles of vitamin E in human health and some diseases as well as the consequences of vitamin E
deficiency. e main focus of the review is on the tocopherol class of the vitamers.
Keywords: Vitamin E; Health; Tocopherols; Antioxidants.
The Role of Vitamin E in Human Health and Some
Saliha Rizvi, *Syed T. Raza, Faizal Ahmed, Absar Ahmad, Shania Abbas, Farzana Mahdi
The Role of Vitamin E in Human Health and Some Diseases
e158 | SQU M J, M , V , I 
of their importance to human health and disease
prevention. e data obtained from a survey of clinical
trials or systematic reviews have been included here
due to the difficulty of proving the efficacy of vitamin
E supplementation, and in order to describe the
evidence-based results.
Chemistry of Vitamin E
e term ‘tocopherol’ signifies the methyl-substituted
derivatives of tocol and is not synonymous with the
term ‘vitamin E’. Natural tocochromanols comprise
two homologous series: tocopherols with a saturated
side chain and tocotrienols with an unsaturated side
chain. Tocopherols and tocotrienols have the same
basic chemical structure, which is characterised by a
long isoprenoid side chain attached at the 2 position of
a 6-chromanol ring, as shown in Figure 1.
Tocotrienols differ from tocopherols in that they
possess a farnesyl rather than a saturated isoprenoid
C16 side chain. Natural tocopherols occur in the
RRR-configuration while the synthetic form contains
eight different stereoisomers and is called all-rac-
alpha-tocopherol. Tocotrienols possess only the
chiral stereocenter at C-2 and naturally occurring
tocotrienols exclusively possess the 2R,3’E,7’E
configuration.5 e receptors and enzymes in the
body are highly stereoselective and interact exclusively
with one of the enantiomers of a chiral molecule in a
process called chiral recognition. As a result, only one
enantiomer has the desired effect on the body, while
the others may have either no effect or an adverse
effect.6 Vitamin E isoforms are not interconvertible
inside the human body.7
Sources and Recommended
Vitamin E is found in various foods and oils. Nuts,
seeds and vegetable oils contain high amounts of
alpha-tocopherol, and significant amounts are also
available in green leafy vegetables and fortified cereals.
Some of the richest sources of vitamin E, along with
their tocopherol content and percent daily values, are
shown in Tables 1 and 2.
No specific recommendations regarding the intake
of vitamin E have been made officially, and the optimal
supplementation dosage of mixed tocopherols is still
undetermined. When obtained from food sources
alone, vitamin E has no documented evidence of
toxicity. However, evidence of pro-oxidant damage
has been found to be associated with supplements, but
usually only at very high doses (for example at >1,000
mg/day).9 e recommended dietary allowances
(RDAs) for vitamin E (alpha-tocopherol) are shown in
Table 3.
Table 1: Vitamin E content in vegetable oils
Oil Alpha-
in mg of tocopherol per 100 g
Coconut 0.5 0 0.6 0.5
(corn) 11.2 60.2 1.8 0
Palm 25.6 31.6 7.0 14.3
Olive 5.1 Trace
amounts 0 0
Peanut 13.0 21.4 2.1 0
Soybean 10.1 59.3 26.4 0
Wheatgerm 133.0 26.0 27.1 2.6
Sunflower 48.7 5.1 0.8 0
Source: Slover HT. Tocopherols in foods and fats.4
Table 2: Selected dietary sources of vitamin E (alpha-
Food and recommended
in mg per
Wheat germ oil, 1 tablespoon 20.3 100
Sunflower seeds, dry roasted,
1 ounce
7.4 37
Almonds, dry roasted, 1
6.8 34
Sunflower oil, 1 tablespoon 5.6 28
Safflower oil, 1 tablespoon 4.6 25
Hazelnuts, dry roasted, 1
4.3 22
Peanut butter, 2 tablespoons 2.9 15
Peanuts, dry roasted, 1 ounce 2.2 11
Corn oil, 1 tablespoon 1.9 10
Spinach, boiled, ½ cup 1.9 10
Broccoli, chopped, boiled,
½ cup
1.2 6
Soybean oil, 1 tablespoon 1.1 6
Kiwifruit, 1 medium 1.1 6
Mango, sliced, ½ cup 0.7 4
Tomato, raw, 1 medium 0.7 4
Spinach, raw, 1 cup 0.6 3
Adapted from: United States Dep artment of Agriculture (USDA),
Agricultural Research Service. USDA National Nutrient Database for
Standard Reference, Release 25.8
Saliha Rizvi, Syed T. Raza, Faizal Ahmed, Absar Ahmad, Shania Abbas and Farzana Mahdi
 | e159
vitamin E supplements in humans were also seen to
increase the under-carboxylation of prothrombin,13
suggesting that vitamin E decreases the vitamin K
status in humans.
Functions of Vitamin E
prevention o f o x i d at i v e s t r e s s
Vitamin E is a potent chain-breaking antioxidant that
inhibits the production of reactive oxygen species
molecules when fat undergoes oxidation and during the
propagation of free radical reactions.14 It is primarily
located in the cell and organelle membranes where it
can exert its maximum protective effect, even when
its concentration ratio may be only one molecule for
every 2,000 phospholipid molecules. It acts as the first
line of defence against lipid peroxidation, protecting
the cell membranes from free radical attack [Figure
2]. Studies have shown that a mixture of tocopherols
has a stronger inhibitory effect on lipid peroxidation
induced in human erythrocytes compared to alpha-
tocopherol alone.15 Due to its peroxyl radical-
scavenging activity, it also protects the polyunsaturated
fatty acids present in membrane phospholipids and
in plasma lipoproteins.16 e tocopheroxyl radicals
formed can either: (1) oxidise other lipids; (2) undergo
further oxidation producing tocopheryl quinones; (3)
form non-reactive tocopherol dimers by reacting with
another tocopheroxyl radical, or (4) be reduced by
other antioxidants to tocopherol.
It has been found that alpha-tocopherol mainly
inhibits the production of new free radicals, while
gamma-tocopherol traps and neutralises the existing
free radicals. Oxidation has been linked to numerous
possible conditions/diseases including: cancer, ageing,
arthritis and cataracts. us, vitamin E might help
prevent or delay the chronic diseases associated with
Interactions with Dietary
Vitamin E is heavily dependent on vitamin C, vitamin
B3, selenium and glutathione. A diet high in vitamin E
cannot have an optimal effect unless it is also rich in
foods that provide these other nutrients. It was found
that a cooperative interaction between vitamin C and
vitamin E is quite probable, while one between vitamin
C and beta-carotene is improbable and one may exist
between vitamin E and beta-carotene.10 Interactions
were also found between thiols, tocopherols and other
compounds which enhance the effectiveness of the
cellular antioxidant defence systems.11
In 2007, reports from the Women’s Health Study
(WHS) demonstrated that vitamin E supplements
decrease the risk of mortality from thromboembolism
and that alpha-tocopherol decreases the tendency
for clotting in normal healthy women.12 In addition,
Table 3: Recommended dietary allowances for vitamin
E (alpha-tocopherol)
Age RDA in mg (IU)
Males Females
0–6 months* 4 (6) 4 (6)
7–12 months* 5 (7.5) 5 (7.5)
1–3 years 6 (9) 6 (9)
4–8 years 7 (10.4) 7 (10.4)
9–13 years 11 (16.4) 11 (16.4)
>14 years
In pregnancy
If lactating
15 (22.4) 15 (22.4)
15 (22.4)
19 (28.4)
RDA = recommended dietary allowances; IU = international units.
*Adequate intake.
Source: Institute of Medicine. Food and Nutrition Board. D ietary
Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids.63
Figure 1: e structures of a tocopherol and tocotrienol.
Adapted from: Colombo ML. An update on vitamin E, tocopherol and tocotr ienol: Perspectives.10
The Role of Vitamin E in Human Health and Some Diseases
e160 | SQU M J, M , V , I 
reactive oxygen species molecules.
protection o f t h e c e l l
Vitamin E increases the orderliness of the membrane
lipid packaging, thus allowing for a tighter packing
of the membrane and, in turn, greater stability to
the cell. In 2011, Howard et al. showed that vitamin
E is necessary for maintaining proper skeletal muscle
homeostasis and that the supplementation of cultured
myocytes with alpha-tocopherol promotes plasma
membrane repair.18 is occurs because the membrane
phospholipids are prominent targets of oxidants and
vitamin E efficiently prevents lipid peroxidation.
Conversely, in the absence of alpha-tocopherol
supplementation, the exposure of the cultured cells
to an oxidant challenge strikingly inhibits the repair.
Comparative measurements reveal that in order to
promote the repair, an antioxidant must associate
with the membranes, as alpha-tocopherol does, or
be capable of alpha-tocopherol regeneration. us,
vitamin E promotes membrane repair by preventing the
formation of oxidised phospholipids that theoretically
might interfere with the membrane fusion events.
r e g u l at i o n o f p l a t e l e t
aggregation an d protein k i n a s e
c a c t i va t i o n
An increase in the concentration of alpha-tocopherol
in the endothelial cells has been found to inhibit platelet
aggregation and to release prostacyclin from the
endothelium. is effect was thought to occur because
of the downregulation of the intracellular cell adhesion
molecule (ICAM-1) and the vascular cell adhesion
molecule (VCAM-1), thereby decreasing the adhesion
of blood cell components to the endothelium. Also, due
to their upregulation by vitamin E in the arachidonic
acid cascade, the increase in the expression of cytosolic
phospholipase A2,19 and cyclooxygenase-1,20 increases
the release of prostacyclin, which is a potent vasodilator
and inhibitor of platelet aggregation in humans.21 A
few other studies suggest that tocopherols appear to
inhibit platelet aggregation through the inhibition of
protein kinase C (PKC)22 and the increased action of
nitric oxide synthase.23
e natural RRR-configuration form of alpha-
tocopherol has been shown to be twice as potent as
the other all-racemic (synthetic) alpha-tocopherols
in inhibiting PKC activity.24 is occurs because of
the attenuating effect of alpha-tocopherol on the
generation of membrane-derived diacylglycerol (a lipid
which facilitates PKC translocation and thus increases
its activity); additionally, alpha-tocopherol increases
the activity of protein phosphatase type 2A, which
inhibits PKC autophosphorylation and, consequently,
its activity. Mixed tocopherols are more effective than
alpha-tocopherol in inhibiting platelet aggregation.
Adenosine diphosphate-induced platelet aggregation
decreased significantly in healthy people who were
given gamma-tocopherol-enriched vitamin E (100 mg
of gamma-tocopherol, 40 mg of delta-tocopherol and
20 mg of alpha-tocopherol per day), but not in those
receiving pure alpha-tocopherol alone (100 mg per
day) or in the controls.25
Vitamin E in Disease
Vitamin E has been found to be very effective in
Figure 2: e mechanism of vitamin E (alpha-tocopherol)-mediated low-density lipoprotein lipid peroxidation.
Adapted from: Rathore GS, Suthar M, Pareek A, Gupta RN. Nutritional antioxidants: A battle for better health.17
Saliha Rizvi, Syed T. Raza, Faizal Ahmed, Absar Ahmad, Shania Abbas and Farzana Mahdi
 | e161
delta-tocopherol has shown growth inhibitory activity
against mouse mammary cancer cell lines.33
Gamma-tocopherol inhibits the growth of cancer
cells in cultures through a number of mechanisms.
It traps free radicals, including the reactive nitrogen
species molecules that cause mutations in the
deoxyribonucleic acid strands and malignant
transformations in the cells.34 It also downregulates
the control molecules known as cyclins, stopping the
cancerous cell cycle in the middle and thus preventing
their proliferation.35 Gamma-tocopherol has also been
found to be superior to alpha-tocopherol in: inducing
apoptosis; triggering a number of cell-death-inducing
pathways;36 stimulating peroxisome proliferator-
activated receptor gamma activity, especially in colon
cancer cells,37 and in reducing the formation of new
blood vessels in tumours, thus depriving them of
the nutrients they need to thrive.38 In this context,
tocotrienols were also found to have antiproliferative
and apoptotic activities on normal and cancerous
cells in humans, which could be due to the induction
of apoptosis by a mitochondria-mediated pathway,
or due to the suppression of cyclin D which would
therefore arrest the cell cycle.39 ey also inhibit
vascularisation and suppress 3-hydroxy-3-methyl
coenzyme A (HMG-CoA) reductase activity, thus
preventing malignant proliferation.
Jiang et al. showed that, of the various forms
of vitamin E, gamma-tocopherol, particularly in
combination with delta-tocopherol, induced apoptosis
in androgen-sensitive prostate cancer cells within
three days of treatment, while alpha-tocopherol alone
did not have the same effect.40 e gamma and delta
E fractions appear to induce apoptosis by interrupting
the synthesis of sphingolipid in the membranes of
human prostate cancer cells.40 e fractions do this by
inducing the release of cytochrome c, the activation
of caspase-9 and caspase-3, the cleavage of poly-
adenosine diphosphate (ADP)-ribose polymerase
(PARP) and the involvement of caspase-independent
pathways. Recently, Chen reported that, of the
tocopherols tested, the gamma form was the most
potent anti-cancer form of the vitamin. ey also
found a novel anti-cancer mechanism of vitamin E:
gamma-tocopherol, they created a new agent which
was found to be 20-fold more effective. ey did so by
removing a string of chemical groups dangling from
the head group of gamma-tocopherol which enhanced
its anti-cancer effect. Chen et al. said that gamma-
tocopherol was more effective than other tocopherols
because of its chemical structure which is more
effective in attaching and thus shutting off the Akt
enzyme.38 ese findings suggest that an agent based
on the chemical structure of one form of vitamin E
the prevention and reversal of various disease
complications due to its function as an antioxidant,
its role in anti-inflammatory processes, its inhibition
of platelet aggregation and its immune-enhancing
cardiovascular diseases
Cardiovascular complications basically arise because
of the oxidation of low-density lipoproteins present in
the body and the consequent inflammation.26 Gamma-
tocopherol is found to improve cardiovascular
functions by increasing the activity of nitric oxide
synthase, which produces vessel-relaxing nitric
oxide.27 It does this by trapping the reactive nitrogen
species (peroxynitriten) molecules and thus enhancing
the endothelial function. Researchers have found that
the supplementation of 100 mg per day of gamma-
tocopherol in humans leads to a reduction in several
risk factors for arterial clotting, such as platelet
aggregation and cholesterol.28 In another study, mixed
tocopherols were found to have a stronger inhibitory
effect on lipid peroxidation and the inhibition
of human platelet aggregation than individual
tocopherols alone,25 suggesting a synergistic platelet-
inhibitory effect. Apart from tocopherols, tocotrienols
were also found to inhibit cholesterol biosynthesis by
suppressing 3-hydroxy-3-methylglutaryl-CoA (HMG-
CoA) reductase, resulting in less cholesterol being
manufactured by the liver cells.29 Contradictory to this,
most of the recent large interventional clinical trials
have not shown cardiovascular benefits from vitamin
E supplementation and report that the use of vitamin
E was associated with a significantly increased risk of
a haemorrhagic stroke in the participants.30 us, it
was suggested that understanding the potential uses of
vitamin E in preventing coronary heart disease might
require longer studies with younger participants.
c a n c e r
Vitamin E also possesses anti-cancer properties. is
is possibly because of the various functions of vitamin
E which include: the stimulation of the wild-type p53
tumor suppressor gene; the downregulation of mutant
p53 proteins; the activation of heat shock proteins, and
an anti-angiogenic effect mediated by the blockage of
transforming growth factor alpha.31 Alpha-, gamma-
and delta-tocopherols have emerged as vitamin E
molecules with functions clearly distinct from each
other in anti-cancer activity as well. Alpha-tocopherol
was found to inhibit the production of PKC and
collagenase,32 which facilitate cancer cell growth. In
this context gamma-tocopherol was found to be more
effective than alpha-tocopherol in its growth inhibitory
effect on human prostate cancer cell lines, whereas
The Role of Vitamin E in Human Health and Some Diseases
e162 | SQU M J, M , V , I 
could help to prevent and treat numerous types of
cancer—particularly those associated with a mutation
in the PTEN gene, a fairly common cancer-related
genetic defect that keeps protein kinase B (Akt) active.
Chen studied both alpha and gamma forms of the
vitamin E molecule; both inhibited the Akt enzyme in
very targeted ways, but the gamma structure emerged
as the more powerful form of the vitamin. In effect,
the vitamin halted Akt activation by attracting Akt
and the PHLPP1 protein to the same region of a cell
where the vitamin was absorbed in the fat-rich cell
membrane. e PHLPP1 tumour suppressor protein
then launched a chemical reaction that inactivated
Akt, rendering it unable to keep cancer cells alive.
Apart from these findings, the role of vitamin
E in cancer prevention remains controversial. e
reports from the Cancer Institute of New Jersey
show that gamma- and delta-tocopherols can prevent
colon, lung, breast and prostate cancers, while alpha-
tocopherol had no such effect. In addition, human
trials and surveys aiming to study the association
between vitamin E intake and cancer have found
that vitamin E is not beneficial in most cases. Both
the Heart Outcomes Prevention Evaluation—e
Ongoing Outcomes (HOPE-TOO) trial and the WHS
study evaluated whether vitamin E supplements might
protect people from cancer and found no significant
reduction in the risk of developing cancer in individuals
taking daily doses of 400 IU or 600 IU of vitamin E.41,42
c at a r a c t s
Cataracts are one of the commonest causes of significant
vision loss in older people. ey basically occur due
to the accumulation of proteins damaged by free
radicals. Several observational studies have revealed a
potential relationship between vitamin E supplements
and the risk of cataract formation. Leske et al. found
that lens clarity was superior in participants who took
vitamin E supplements and those with higher blood
levels of the vitamin.43 In another study, a long-term
supplementation of vitamin E was associated with the
slower progression of age-related lens opacification.44
However, in the randomised Age-Related Eye Disease
Study (AREDS), vitamin E had no apparent effect on
cataract development/progression over an average
of 6.3 years.45 Overall, the available evidence is
insufficient to conclude that vitamin E supplements,
taken alone or in combination with other antioxidants,
can reduce the risk of cataract formation.
alzheimers disease
Alzheimer’s disease (AD) occurs as a result of protein
oxidation and lipid peroxidation via a free radical
mechanism, where the beta amyloid protein induces
cytotoxicity through a mechanism involving oxidative
stress and hydrogen peroxide, leading to neuronal
cell death and, finally, AD. Vitamin E can block the
production of hydrogen peroxide and the resulting
cytotoxicity. It reduces beta amyloid-induced cell death
in rat hippocampal cell cultures46 and PC12 cells47 and
attenuates the excitatory amino acid-induced toxicity
in neuroblastoma cells.48 e Alzheimer’s Disease
Cooperative Study in 1997 showed that vitamin E may
slow disease progression in patients with moderately
severe AD. High doses of vitamin E delayed the loss
of the patient’s ability to carry out daily activities
and their consequent placement in residential care
for several months.49 In another study, it was found
that subjects with AD had reduced concentrations
of plasma antioxidant micronutrients, suggesting
that inadequate antioxidant activity is a factor in this
disease. High plasma levels of vitamin E are associated
with a reduced risk of AD in older patients and this
neuroprotective effect is related to the combination
of different forms of vitamin E rather than to alpha-
tocopherol alone.50 A study published in 2009 examined
the effects of taking 2,000 IU of vitamin E with and
without an AD drug on 847 people. It concluded that
vitamin E plus a cholinesterase inhibitor may be more
beneficial than taking either agent alone.51
At the biomarker level, Mangialasche et al.
demonstrated that plasma levels of tocopherols and
tocotrienols together with automated magnetic
resonance imaging (MRI) measures can help to
differentiate patients with AD and mild cognitive
impairment (MCI) from the control subjects, and
prospectively predict the MCI conversion into AD.49
is therefore suggests the potential role of nutritional
biomarkers detected in plasma-tocopherols and
tocotrienols as indirect indicators of AD pathology.52
However, researchers have recommended that
patients should not take vitamin E to treat AD without
the supervision of a physician, as in high doses it can
interact negatively with other medications, including
those prescribed to lower cholesterol.
human immunodeficiency virus
a n d acquired immunodeficiency
Vitamin E is an important anti-inflammatory
agent that is often found to be deficient in human
immunodeficiency virus (HIV)-positive individuals;
however, it is not known whether vitamin E
supplementation is beneficial either at every or any
stage of HIV infection. At a dose of 400 IU, vitamin
E was shown to restore delayed skin hypersensitivity
reactions and interleukin-2 production, and at high
doses it was shown to stimulate T helper cell (CD4
Saliha Rizvi, Syed T. Raza, Faizal Ahmed, Absar Ahmad, Shania Abbas and Farzana Mahdi
 | e163
or acquired condition that impairs their ability to
absorb the vitamin (for instance, cystic fibrosis, short
bowel syndrome or bile duct obstruction) and in those
who cannot absorb dietary fat or have rare disorders
of fat metabolism. Recent reports have shown that the
alpha-TTP regulates the secretion of alpha-tocopherol
from the liver cells and that missense mutations of
some arginine residues at the surface of the alpha-
TTP can cause severe vitamin E deficiency in
humans.63 e wild-type alpha-TTP was found to bind
phosphatidylinositol phosphates (PIPs), whereas the
arginine mutants did not—where the PIPs in the target
membrane promoted the inter-membrane transfer
of alpha-tocopherol by alpha-TTP. e resulting
symptoms of vitamin E deficiency include muscle
weakness, vision problems, immune system changes,
numbness, difficulty in walking and tremors as well as
a poor sense of balance. Apart from these symptoms,
deficiency can also lead to neuromuscular problems
such as spinocerebellar ataxia and myopathies,24
dysarthria, an absence of deep tendon reflexes, the
loss of both vibratory sensations and positive Babinski
reflexes.24 Vitamin E deficiency can also cause anaemia
due to the oxidative damage to the red blood cells,24
retinopathy64–67 and the impairment of the immune
response.59–61 If untreated, vitamin E deficiency may
result in blindness, heart disease, permanent nerve
damage and impaired thinking. Some reports also
suggest that vitamin E deficiency can even result in
male infertility.24
Vitamin E was first used as a supplement in Canada by
the physicians Shute and Shute; based on the positive
results it achieved, they began using it regularly in their
practices. Since then, well-designed experimental and
clinical studies have progressed steadily and increased
our knowledge of vitamin E. e antioxidative
properties of vitamin E have been found to play a
vital role in the battle against various diseases such as
atherosclerosis, oxidative stress, cancer, cataract and
AD, among others.
is review focussed on the important functions
of vitamin E in some diseases; in addition to these, this
vitamin has been found to be effective against asthma,
allergies and diabetes, among others. Discussion
of the dietary sources, RDA and the interaction of
vitamin E supplements with other dietary factors, has
demonstrated the need for and significance of vitamin
E in the human context. us, raising public awareness
of the role of dietary antioxidants in maintaining better
health would benefit a number of lives.
T-cell) proliferation.53 In 1997, Tang et al. studied the
association between serum vitamin A and E levels with
HIV-1 disease progression. In this study, it was found
that men with serum vitamin E levels above 23.5 µm/L
had a significantly reduced risk of disease progression.
A strong correlation was noted in this cohort between
the intake of supplements containing vitamin E at the
point of entry into the study and high blood levels of
vitamin E.54
A study on murine acquired immunodeficiency
syndrome (AIDS) using a 15-fold increase in dietary
vitamin E showed the normalisation of immune
parameters that are altered in HIV/AIDS.55 Apart
from this, an increase in dietary vitamin E has also
been shown to protect against the side-effects of
azidothymidine, such as bone marrow toxicity.56 Related
studies on bone marrow cultures from stage IV AIDS
patients using d-alpha-tocopherol supplementation
revealed similar results.57 Nevertheless, it has also been
reported that higher vitamin E levels pre-infection
were found to be associated with increased mortality.
us, further research is needed to elucidate the role
vitamin E plays in the pathogenesis of HIV-1.58
i m m u n i t y
It has now been proven that vitamin E stimulates the
body’s defences, enhances humoral and cell immune
responses and increases phagocytic functions. It has
a pronounced effect in infectious diseases where
immune phagocytosis is involved, but is less effective
in the case of cell-mediated immune defences. Its
supplementation significantly enhances both cell-
mediated and humoral immune functions in humans,
especially in the elderly. A daily intake of 200 mg of
vitamin E improved the antibody response to various
vaccines in healthy subjects who showed no adverse
side-effects to vitamin E supplementation.59 Vitamin
E also enhanced resistance to viral diseases in elderly
subjects, where higher plasma vitamin E levels
correlated with a reduced number of infections over
a three-year period.60 A recent study by Kutty et al.
showed that a daily supplementation of vitamin E can
enhance the immune response to a specific antigen.61
Besides the above mentioned diseases, vitamin E
has also been found to play a beneficial role in other
diseases, such as photodermatitis, menstrual pain/
dysmenorrhoea, pre-eclampsia and tardive dyskinesia,
when taken along with vitamin C.62
Vitamin E Deficiency
Vitamin E deficiency is quite rare in humans. It
happens almost exclusively in people with an inherited
The Role of Vitamin E in Human Health and Some Diseases
e164 | SQU M J, M , V , I 
Apart from the enormous benefits reported, there
has always been debate about the exact function of
vitamin E and its role in various diseases. ere are
many conflicting reports of positive and negative
results on the same biological activities in the
literature. e primary hindrance in determining
the roles of vitamin E in human health is the lack
of validated biomarkers for vitamin E intake and
status, which would help to relate intakes to possible
clinical outcomes. In conclusion, although the data
surrounding vitamin E is contradictory, the current
literature appears to support the view that the benefits
outweigh the side-effects.
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... Research has shown that missense mutations of some arginine residues at the surface of the α-TPP can induce severe vitamin E deficiency in humans. This study revealed that phosphatidylinositol phosphates (PIPs) in the target membrane promote the transfer of α-tocopherol by binding to the wild type of α-TPP, but this activity is lost with an arginine mutant α-TPP [55]. ...
... It could lead to neurodegenerative diseases presenting as myopathies, spinocerebellar ataxia, dysarthria, diminished deep tendon reflexes, absence of both vibratory sensations and positive Babinski reflexes, and impaired thinking. Oxidative damage to the red blood cells precipitates severe hemolytic anemia, adversely affecting the immune system [55,56]. ...
Full-text available
Studies in the last two decades show the relationship between malnutrition and the debility of some diseases. While some scholars believe it contributes to the virulence of infectious diseases, others opine that it plays a role in the deteriorating conditions of some metabolic or noncommunicable diseases. In recent times, the term malnutrition has been expanded to cover a broader spectrum, ranging from the double burden, which includes undernutrition and overnutrition, to the triple burden, in which the duo and micronutrient deficiency are considered. This review elaborates on the broader definition of malnutrition, the determinants of malnutrition, the triple burden of malnutrition coupled with the tandem effects of malnutrition on the immune system. Where possible, we used examples to clarify and conceptualize this review, bringing in some real-life context in which these burdens are applicable. We discussed the cellular implications of the micronutrient deficiencies and buttressed using body mass index as a rough guide in estimating overweight and underweight.
... Centrifugation was carried out for five minutes [14] [13] [16]. Three millilitres was transferred into triplicate tubes and allowed to evaporate to dryness. ...
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Medicinal plants continue to show a dominant role in the healthcare system and this is mainly true in developing countries, where herbal medicine has continuous history of long use. This research was designed to determine the vitamin composition of ethanol leaf extract of Rauwolfia vomitoria. Vitamins as organic compounds that are needed in small quantities to sustain life were present in high concentration and were determined using standard method. The result of vitamin composition showed that ethanol leaf extract of Rauwolfia vomitoria is rich in vitamins
... A recent bioinformatics study showed that this compound could bind to the host cell surface receptor, thereby reducing the binding of the SARS-CoV-2 virus 11 . Vitamin E, a lipidsoluble compound, plays a vital role in the battle against atherosclerosis, oxidative stress, cancer, arthritis, cataract, asthma, allergies and diabetes 31 . It was reported that 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-has the ability to kill the microbes and reduce inflammation 18 . ...
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About 40 to 90% of the population in many developing countries uses traditional medicine. The use of traditional medicine is increasing in developing countries because of the high cost and fear of side effects of allopathic medicine. Especially for treating lifestyle diseases like diabetes, the number of people adopting traditional medication is increasing yearly. Bitter gourd is grown in tropical and subtropical regions and is one of the important plant species used for treating diabetes due to its antidiabetic, anti-lipidemic and antioxidant properties. Fruits of bitter gourd are the main plant parts used for treating diabetes. Bitter gourd fruits are used as a vegetable and consuming them regularly is likely to help in diabetes management with less drug dependency. However, the bitter taste of the fruits is deterrent. Between Momordica charantia var. charantia and Momordica charantia var. muricata, muricata is relatively less bitter. In this study, we extracted the secondary metabolites from the outer rind, inner pulp and seeds from the fruits of both varieties and profiled them by GC-MS analysis. We identified several secondary metabolites and for some of them, biological activities were reported earlier. Identification of these compounds supported the medicinal properties of bitter gourd and formed the basis for the characterization of purified compounds in the future.
... Deviation from normality in vitamin levels may result in the following medical complications: (a) age-related deficiency in vitamin D (14) manifests itself as an increased rate of bone fracture, (b) a deficiency in vitamin B12 (15) increases the risk of osteoporosis, cardiovascular diseases, a decrease in cognitive dysfunction, and dementia, (c) low level of vitamin C (16) leads to a decrease in collagen synthesis, resulting in increased fragility of blood vessels and arterial stiffness, (d) a lower level of vitamin E (17, 18) increases the risk of atherosclerosis, oxidative stress, cancer, cataract, and Alzheimer's disease. ...
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Aging is an independent risk factor for the development of various diseases associated, among others, with detrimental blood levels of fat- and water-soluble vitamins. Thus, the objective of this study is to investigate age-related changes in blood levels of vitamin A, B12, C, D, and E. Subject serum vitamin levels were obtained from the combined National Health and Nutrition Examination Surveys (NHANES). NHANESIII and NHANES 1999–2000, 2001–2002, 2003–2004, and 2005–2006. The raw data set was stratified into five age groups G1- G5: 20 ≤ G1 < 30, 30 ≤ G2 < 40, 40 ≤ G3 < 50, 50 ≤ G4 < 60, and 60 ≤ G5 < 70 years of age. Age stratified data was cleaned using the modified Horn algorithm. The reference range for the vitamin level of a specific age group was defined as data between the first and third quartile of the subject defined by normal blood pressure and normal bone density. Age-dependent changes in serum/plasma vitamin levels were assessed using the bootstrap technique with 10,000 repeats and Bonferroni adjustment. There was a continuous increase in vitamin A, B12, D, and E levels in the blood. However, the vitamin C concentration remained virtually constant in all age groups. There was a lack of cross-correlations between lipid and water-soluble vitamin levels and blood pressure and bone health. The following reference levels for vitamin A, B12, C, D, and E in subjects older than 20 years of age were established: vitamin A: 1.32–2.8 mmol/L, vitamin B12: 257.94–498.33 pmol/L, vitamin C: 38.18–79.2 mmol/L, vitamin D: 76.33–199.36 nmol/L and vitamin E: 3.65–41.12 μmol/L.
... In addition, vitamin C has been reported to attenuate lipid peroxidation in the cellular membranes by scavenging the peroxyl radical, thus leading to improved antioxidant properties of vitamin E [131]. The latter (vitamin E) is classified as a fat-soluble vitamin that is divided into different tocopherols that display enhanced antioxidant properties [133]. A study performed on postmenopausal women with T2D, showed that combined effect of vitamin C and E could significantly improve intracellular antioxidant levels and other metabolic parameters such as lipid profiles and glucose control [134]. ...
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Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q10, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.
... A similarly purposed study also related the intake of the vitamin to improved outcomes in mice infected with the influenza virus [164]. The role of vitamin E in human immunodeficiency virus (HIV) was also required to unravel the potential anti-viral effects of its intake [165]. Additionally, the Newcastle disease virus (NDV) is another viral infection where vitamin E was identified to have a great dietary potential due to its regressive effects on the manifestations of the disease [166]. ...
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COVID-19 is a recent pandemic that mandated the scientific society to provide effective evidence-based therapeutic approaches for the prevention and treatment for such a global threat, especially to those patients who hold a higher risk of infection and complications, such as patients with autoimmune diseases and cancer. Recent research has examined the role of various fat-soluble vitamins (vitamins A, D, E, and K) in reducing the severity of COVID-19 infection. Studies showed that deficiency in fat-soluble vitamins abrogates the immune system, thus rendering individuals more susceptible to COVID-19 infection. Moreover, another line of evidence showed that supplementation of fat-soluble vitamins during the course of infection enhances the viral clearance episode by promoting an adequate immune response. However, more thorough research is needed to define the adequate use of vitamin supplements in cancer and autoimmune patients infected with COVID-19. Moreover, it is crucial to highlight the vitamin–drug interactions of the COVID-19 therapeutic modalities and fatsoluble vitamins. With an emphasis on cancer and autoimmune patients, the current review aims to clarify the role of fat-soluble vitamins in SARS-CoV-2 infection and to estimate the risk-to-benefit ratio of a fat-soluble supplement administered to patients taking FDA-approved COVID-19 medications such as antivirals, anti-inflammatory, receptor blockers, and monoclonal antibodies.
Pemanfaatan keanekaragaman hayati flora masih sangat potensial dieksplorasi sebagai sumber obat. Salah satu penggunaan fitokimia adalah pemanfaatannya sebagai imunomodulator untuk membantu imunitas tubuh memerangi agen infeksius. Tanaman bayam Brasil mempunyai potensi untuk dikembangkan sebagai salah satu imunostimulan berbasis herbal karena nilai nutrisi dan senyawa fitokimia yang dikandungnya. Penelitian ini bertujuan untuk mempelajari efek ekstrak daun bayam Brasil terhadap respon imun mencit jantan dilihat dari jumlah limfosit dan nilai indeks limpa dan timus. Ekstrak daun bayam Brasil diperoleh dengan metode maserasi menggunakan pelarut etanol 96%. Deteksi fitokimia menggunakan metode biokimia kualitatif dan GC-MS. Uji in vivo dilakukan dengan memberikan 6 perlakuan pada mencit jantan peroral dalam 7 hari yaitu perlakuan akuades, kontrol negatif (Na-CMC-akuades), kontrol positif (imunostimulan komersil), dan tiga dosis ekstrak daun bayam Brasil yaitu 0,1563 mg/g BB; 0,312 mg/g BB), dan 0,468 mg/g BB. Jumlah limfosit dipreparasi dan dihitung dengan apusan darah, serta penghitungan indeks limpa dan timus berbasis perhitungan berat segar. Hasil identifikasi biokimia kualitatif menunjukkan kandungan flavonoid, alkaloid, saponin, tanin dan steroid dalam ekstrak daun bayam Brasil. Analisis GC-MS menunjukkan 3 senyawa dominan yaitu neophytadiene, phytol dan ?-Tocopheryl acetate. Pemberian ekstrak daun bayam Brasil dengan dosis 0,1563 mg/g BB paling efektif meningkatkan jumlah limfosit hewan uji. Nilai indeks timus dan limpa berkorelasi dengan meningkatnya jumlah limfosit pada pemberian ekstrak daun bayam Brasil. Hasil ini menunjukkan potensi dasar penggunaan daun bayam Brasil sebagai imunostimulan
Epidemics and pandemics have always been pulling down on human existence. Currently, we are facing the pandemic of COVID-19 caused by the SARS-CoV-2 virus. The existing treatment options for this virus affecting the respiratory tract fall short. Such viruses take advantage of their evolutionary benefit of evading the host immune responses to establish infection in the host. Thus, a patent immune system of the host is a must to tackle such infections. A vigilant immune system will identify the virus cells present in the host and try to contain the infection from spreading to other parts of the body by phagocytosing it with the help of specialized cells like macrophages, neutrophils, dendritic cells, etc. Antigen presenting cells present the viral peptides to the cytotoxic T cells to initiate the cascade of events leading to the formation of antibodies against the virus and clearing of the infection from the body. Viruses interfere with both the innate and adaptive immune responses to circumvent the host immunity. Evading the antigen presentation and molecular mimicry to subdue the cytokines are some of the mechanisms exhibited by viruses. Effective recuperation of health needs a “healthy” immune system and for this the most effective way is to utilize the plethora of chemical entities belonging to the nutraceuticals. Vast researches undergoing in the field of nutraceuticals adds sufficient evidence on their antiviral properties. This wisdom helps to use nutraceuticals as adjunctive therapies along with the conventional treatment regimes.
annually in Europe, 4 million people die from cardiovascular diseases, the main cause of which is atherosclerosis. In order to slow down the development of atherosclerotic plaques, the main therapeutic goal is to lower LDL cholesterol (LDL-C) level. Undoubtedly, statins are the basis of lipid-lowering therapy for many years. However, a European study shows that only 43% of statin-taking patients achieved their LDL-C targets. PCSK9 inhibitors are a new group of lipid-lowering drugs whose main point of action is the protein discovered in 2003 – the PCSK9 (proprotein convertase subtilisin/kexin 9). This protein is responsible for reducing the density of LDL receptors on the surface of hepatocytes, which increases the value of LDL-C. The discovery of this protein was soon after the basis for the start of research, thanks to which three monoclonal antibodies against PCSK9 were developed - evolocumab, alirocumab, bococizumab - and inclisiran, an inhibitor of PCSK9 synthesis in the liver. In addition to the mechanism of action of PCSK9 inhibitors, resulting in lowering LDL-C level, a number of pleiotropic mechanisms have also been identified, including effects on metabolic processes and inflammation. Until the registration and introduction of above-mentioned drugs into everyday clinical practice, many studies were carried out, in which, in addition to assessing the effectiveness of treatment, the safety and tolerability of the drug were also examined. The purpose of this review is to summarize information on the safety profile of PCSK9 inhibitors, which may help in making therapeutic decision.
Background: Urinary tract infection (UTI) is among the most common infections in children and acute pyelonephritis (APN) is the most important type of UTI. Late diagnosis and treatment of APN can result in severe complications. This study aimed to evaluate the effect of vitamin E on renal scars in children aged three months to 14 years. Methods: This single-blinded randomized clinical trial (RCT) included all children aged three months to 14 years admitted to tBandar Abbas Children’s Hospital, Bandar Abbas, Iran due to APN in 2017-2018. Patients with renal scars were alternately randomized into two groups. The control group included 41 patients who received 50-75 mg/kg/d intravenous ceftriaxone during hospital stay and the intervention group included 37 cases who received 20 U/kg/d vitamin E tablets in addition to the previous treatment for a total duration of 4 months. Dimercaptosuccinic acid (DMSA) scan was performed at baseline and at the end of 4 months. Results: Out of a total of 78 patients, 34 (43.6%) were boys. Participants of both groups were comparable regarding age and gender. The median of decrease in photopenic areas was insignificantly higher in girls in the vitamin E group compared to girls in the control group (1.26 vs. 1.17, P=0.459). Regardless of gender, decrease in photopenic areas was insignificantly higher in patients aged 1-3 years in the vitamin E group compared to those in the control group (1.40 vs. 1.22, P=0.451). Conclusion: Treatment with vitamin E for at least 4 months may reduce renal scarring in children aged 1-3 years and girls with APN.
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This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response.
Background: Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract. Objective: To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss. Design: The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale. Main Outcome Measures: Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (greater than or equal to 15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P = .01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P = .55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment. Conclusion: Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.
The release of arachidonic acid is the rate limiting in eicosanoid synthesis. Several enzymatic pathways can lead to the release of arachidonic acid. However the 85 kD cytosolic phospholipase A2 (cPLA)2 is now considered as the key protein that is responsible for the release reaction because it demonstrates specific acyl selectivity for the arachidonate containing phospholipids. We have previously reported that vitamin E enrichment potentiated arachidonic acid release as well as spontaneous prostacyclin release inhuman endothelial cells. In the present study we sought to determine the mechanism by vitamin E exerts this effect. When bovine endothelial cells were incubated with different concentrations of vitamin E in the culture medium for 18 hr, the incorporation of cellular vitamin E was dose-dependent. Determination of arachidonate release after labelling cells with [3H] arachidonate showed that vitamin E enrichment caused a dose-dependent increase in ionophore A23187-induced arachidonic acid release. Determination of cytosolic PLA2 activity further demonstrated an increase in enzyme activity due to vitamin E enrichment. Western blot analysis for cPLA2 protein revealed that vitamin E caused an increase in enzyme mass. When prostacyclin synthesis was assessed with the addition of exogenous arachidonic acid, vitamin E enrichment elicited a stimulatory effect on prostacyclin synthesis. Analysis of cyclooxygenase by Western blot showed that vitamin E enriched cells had a higher cyclooxygenase mass. Collectively these data demonstrated that vitamin E potentiated arachidonic acid release is mediated by up-regulating the expression of cPLA2 protein. In addition, vitamin E also has a distinct effect in activating the expression of cyclooxygenase enzyme, thereby increasing the prostacyclin synthetic potential. These results suggest that vitamin E enrichment could be beneficial in reducing thrombosis formation in vivo through increasing the synthesis of an antiaggregating and vasodilating molecule.
α-Tocopherol (vitamin E) transfer protein (α-TTP) regulates the secretion of α-tocopherol from liver cells. Missense mutations of some arginine residues at the surface of α-TTP cause severe vitamin E deficiency in humans, but the role of these residues is unclear. Here, we found that wild-type α-TTP bound phosphatidylinositol phosphates (PIPs), whereas the arginine mutants did not. In addition, PIPs in the target membrane promoted the intermembrane transfer of α-tocopherol by α-TTP. The crystal structure of the α-TTP–PIPs complex revealed that the disease-related arginine residues interacted with phosphate groups of the PIPs and that the PIPs binding caused the lid of the α-tocopherol–binding pocket to open. Thus, PIPs have a role in promoting the release of a ligand from a lipid-transfer protein.
Peroxynitrite, a powerful mutagenic oxidant and nitrating species, is formed by the near diffusion-limited reaction of \cdot NO and O2{\cdot} during activation of phagocytes. Chronic inflammation induced by phagocytes is a major contributor to cancer and other degenerative diseases. We examined how γ -tocopherol (γ T), the principal form of vitamin E in the United States diet, and α -tocopherol (α T), the major form in supplements, protect against peroxynitrite-induced lipid oxidation. Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the \cdot NO and O2{\cdot} generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by γ T than α T. More importantly, nitration of γ T at the nucleophilic 5-position, which proceeded in both liposomes and human low density lipoprotein at yields of ≈ 50% and ≈ 75%, respectively, was not affected by the presence of α T. These results suggest that despite α T's action as an antioxidant γ T is required to effectively remove the peroxynitrite-derived nitrating species. We postulate that γ T acts in vivo as a trap for membrane-soluble electrophilic nitrogen oxides and other electrophilic mutagens, forming stable carbon-centered adducts through the nucleophilic 5-position, which is blocked in α T. Because large doses of dietary α T displace γ T in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily α T should be reconsidered.