role of anti oxidant
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Role of Antioxidants in Cardiovascular diseases 2012
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INTRODUCTION:
An Antioxidant is a molecule capable of inhibiting the oxidation of
other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a
substance to an oxidizing agent. Oxidation reactions can produce reactive oxygen species
(ROS). The generation of reactive oxygen species (ROS) is an inevitable consequence of life
in an aerobic environment. ROS are characterised by their high chemical reactivity and
include both free radicals (that is, species with one or more unpaired electrons, such as
superoxide (O2.
) and hydroxyl radicals (OH.)), and non-radical species such as hydrogen
peroxide (H2O2). In health, there is a balance between ROS generation and the activity of
enzymatic and non-enzymatic antioxidant systems that scavenge or reduce ROS
concentrations. In turn, these radicals can start chain reactions. When the chain reaction
occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain
reactions by removing free radical intermediates, and inhibit other oxidation reactions. Redox
imbalance caused by increased ROS production and/or reduced antioxidant reserve causes
oxidative stressthat is, an enhanced susceptibility of biological molecules and membranes
to reaction with ROS.
Traditionally, oxidative stress has been considered deleterious due to free radical induced
oxidation and damage of macromolecules, membranes and DNA. ROS generation by
phagocytic cells such as neutrophils is a pivotal component of their antimicrobial actions and
as such deleterious for ingested organisms, but is, however, clearly beneficial for the host. On
the other hand, the restoration of oxygen supply during myocardial reperfusion after
prolonged ischemia is accompanied by a burst of free radical production that is damaging for
the heart. Oxidative stress induced damage includes acceleration of cell death through
apoptosis and necrosis, mechanisms that may also be of relevance in advanced heart failure.
They do this by being oxidized themselves, so antioxidants are often reducing agents such
as vitamins, phytochemicals, minerals or polyphenols.
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Classification of Antioxidants:
I. Endogenous Antioxidants (cellular antioxidant- made in the body)
Glutathione CoQ10 Alpha Lipoic Acid
II. Exogenous Antioxidants
1) Vitamins
Vitamin C
Vitamin E
2) Phytochemicals - photosynthetic nutrients/ plant pigments.
a. Carotenoids - best known as precursor of Vit. A
-carotene, -carotene, lycopene, lutein, zeaxanthin
b. Bioflavonoids or flavonoids - another type of plant pigment,
Major classes are:
Flavonones Flavonols Isoflavones
3) Minerals
Selenium Zinc
4) Hormone:
Melatonin
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I. Endogenous Antioxidants:
1) GLUTATHIONE: (The Master Antioxidant)
Glutathione (GSH) is a tripeptide that contains an unusual peptide linkage between the amine
group ofcysteine (which is attached by normal peptide linkage to a glycine) and
the carboxyl group of the glutamate side-chain. It is an antioxidant, preventing damage to
important cellular components caused
by reactive oxygen species such as free
radicals and peroxides.
BIOSYNTHESIS OF GLUTATHIONE:
Glutathione is not an essential
nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the
body from the amino acidsL-cysteine, L-glutamic acid, and glycine. The sulfhydryl (thiol)
group (SH) of cysteine serves as a proton donor and is responsible for the biological activity
of glutathione. Provision of this amino acid is the rate-limiting factor in glutathione synthesis
by the cells, since cysteine is relatively rare in foodstuffs. Furthermore, if released as the free
amino acid, cysteine is toxic and spontaneously catabolized in the gastrointestinal tract and
blood plasma.[4]
Glutathione is synthesized in two adenosine triphosphate-dependent steps:
First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via theenzyme gamma-glutamylcysteine synthetase (a.k.a. glutamate cysteine ligase, GCL).
This reaction is the rate-limiting step in glutathione synthesis.[5]
Second, glycine is added to the C-terminal ofgamma-glutamylcysteine via theenzyme glutathione synthetase.
As electrons are lost, the molecule becomes oxidized, and two such molecules become linked
(dimerized) by a disulfide bridge to form Glutathione disulfide or oxidized Glutathione
(GSSG). This linkage is reversible upon re-reduction.
Glutathione.
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Glutathione is under tight homeostatic control both intracellularly and extracellularly. A
dynamic balance is maintained between GSH synthesis, its recycling from GSSG/oxidized
Glutathione, and its utilization.
Glutathione is used as a cofactor by (1) multiple peroxidase enzymes, to detoxify peroxides
generated from oxygen radical attack on biological molecules; (2) transhydrogenases, to
reduce oxidized centers on DNA, proteins, and other biomolecules; and (3) Glutathione S-
transferases (GST) to conjugate Gluathione with endogenous substances (e.g., estrogens),
exogenous electrophiles (e.g., arene oxides, unsaturated carbonyls, organic halides), and
diverse xenobiotics. Low GST activity may increase risk for diseasebut paradoxically,
some Glutathione conjugates can also be toxic.
Direct attack by free radicals and other oxidative agents can also deplete Glutathione. The
homeostatic Glutathione redox cycle attempts to keep Glutathione repleted as it is being
consumed. Amounts available from foods are limited (less that 150 mg/day), and oxidative
depletion can outpace synthesis.
The liver is the largest Glutathione reservoir. The parenchymal cells synthesize GSH for
P450 conjugation and numerous other metabolic requirementsthen export GSH as a
systemic source of SH-reducing power. Glutathione is carried in the bile to the intestinal
luminal compartment. Epithelial tissues of the kidney tubules, intestinal lining and lung have
substantial P450 activityand modest capacity to export Glutathione.
Mechanism of Action:
Glutathione is an extremely important cell protectant. It directly quenches reactive hydroxyl
free radicals, other oxygen-centered free radicals, and radical centers on DNA and other
biomolecules. Glutathione is a primary protectant of skin, lens, cornea, and retina against
radiation damage and other biochemical foundations of P450 detoxification in the liver,
kidneys, lungs, intestinal, epithelia and other organs.
Glutathione is the essential cofactor for many enzymes that require thiol-reducing
equivalents, and helps keep redox-sensitive active sites on enzyme in the necessary reduced
state. Higher-order thiol cell systems, the metallothioneins, thioredoxins and other redox
regulator proteins are ultimately regulated by Glutathione levelsand the GSH/GSSG redox
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ratio. GSH/GSSG balance is crucial to homeostasisstabilizing the cellular biomolecular
spectrum, and facilitating cellular performance and survival.
Glutathione is your body's master antioxidant and one of the most important healing agents.
The highest concentration of glutathione is found in the liver which is the principal organ
involved in the detoxification and elimination of toxic materials. Interestingly, glutathione
also acts to reconstitute the antioxidant vitamins C and E after they have been oxidized, and
therefore plays a determinant role in their function.
No other antioxidant is as important to overall health as glutathione. It is the regulator and
regenerator of immune cells and the most valuable detoxifying agent in the human body.
The Role of GSH in Heart Disease
GSH is the principal antioxidant in our cells. This applies to the endothelial cells of the
arteries, including every red blood and platelet cell.
As a result, fighting oxidative damage by raising your GSH levels may help prevent the
following complications of heart disease:
o heart attack & strokeo protect the lining of the arterieso diminish oxidation of cholesterol
Arteriosclerosis
This is the process of your arteries hardeningoften ending with the big one a heart attack
or stroke. Even the lesser consequences are disasterous high blood pressure and impaired
circulationslowly depriving vital organs and muscles of oxygen.
It is believed that without the anti-oxidant protection benefit of GSH to combat free radicals
and lipid peroxidation, our vascular systems cannot overcome arteriosclerosis.
Arteriosclerosis, previously thought of as an old age' condition, has now been conclusively
linked to diet, smoking and lifestyle issues.
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University of Louisiana researchers found overweight children ages 6 through fifteen years,
in the beginning to advanced stages of arteriosclerosis. It is now common for 30-year-old
persons to suffer significant damage.
Reduction of intracellular glutathione levels produces sustained arterial narrowing', found
convincing evidence that low GSH levels allow free radical damage to go unchecked
narrowing the arteries. It depends where arteriosclerosis develops as to where you feel the
outcome.
1) The pain of angina comes from blocked blood flow.2) If a major artery to the neck or brain becomes narrowedyou're primed for a
stroke.
3) If the arteries to your kidneys become narrowedyou're on the path to kidneyfailure.
4) If the blockage is in your leg poor circulation could lead to fatigue, musclecrampseven gangrene.
However, the process of fatty deposits sticking to inflexible arteries is literally a gradual
buildup' - this entire insidious processcan culminate in one sudden event. No warning.
Cholesterol
The prevention of LDL cholesterol from oxidizing (turning rancid) should be a priority if you
have high cholesterol readings.
GSH is the cells endogenous antioxidant thus it's your body's principal mechanism for
combating the oxidation of fats, known as lipid peroxidation. The process that creates rancid
cholesterol deposits - that stick to your artery walls.
Lipid peroxidation in-turn creates even more oxidative damage and subsequent hardening of
your arteries - giving you the disastrous consequences of arteriosclerosis.
Increased GSH levels have been shown to reduce overall cholesterol levels by raising the
activity of the enzyme cholesterol hydroxylase.
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The British Journal of Nutrition published researchers X. Zhang and A.C. Beynen's, found
that by restoring the level of glutathione in the liver the liver inhibited the synthesis of
cholesterolthereby, lowering a persons cholesterol level.
In a double blind study, P.V. Luoma's team was able to improve the ratio of HDL (good) to
LDL (bad) cholesterol in healthy subjects by raising GSH levels.
An Italian research group had similar success altering HDL to LDL cholesterol ratios by
boosting the GSH levels in patients. Other researchers continue to confirm the link between
low GSH levels - and the epidemic of high' and bad' cholesterol - and the progression to
heart disease.
Statins
GSH has been shown to lower cholesterol - by naturally inhibiting the production of
cholesterol in the liver.
Yet, the current cholesterol-blockers known as Statins - interfere with an enzyme needed for
cholesterol production.While lowering overall cholesterol levels, statin drugs have known
side effects, such as liver damage and arthritis. In addition, weight gain, insomnia, migraine,eye hemorrhage, fatigue, impotence and breast enlargement and impotence in men, and hair
loss in women, are also commonly reported.
American Journal of Medicine, December 1, 2004, reports that a new side effect is reduction
in mental and memory functions. A team of researchers at the University of Pittsburgh has
found that statin drugs reduce brain levels of an essential fatty acid, known as Omega-3.
Heart Attack
Similar to glutathione's protective role in a stroke, when there is adequate GSH within the
cells, the damage from a heart attack is kept to a minimum dramatically increasing your
odds of a better outcome.
A study published in the New England Journal of Medicine, and reported by USA Today,
was so conclusive on the link between low GSH levels and heart attack it stated, low
levels of glutathionesuggest a coming heart attack.
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According to the report, by measuring GSH blood levels, doctors will now have a way to
diagnose an imminent heart attack and act to prevent it.
The Japan Heart Journal published a study that measured the red blood cell GSH count in
patients with heart attacksthey found an evident GSH depletion. This joins the mountain of
scientific evidence pointing to a heart eventas presenting major demands for GSH.
Surgical Procedures
When the blood flowing to your heart is suddenly blocked, the heart muscle is deprived of
oxygen. Some heart cells are irreversibly injured and stop working. Your heart has been
attacked.
During the time when the heart cells aren't getting any oxygen (ischemia stage), they undergo
a free radical build up. When the blockage is surgically cleared - blood floods back into the
injured tissue bringing new oxygen - creating further unrestrained free radical damage
(reperfusion injury). This occurs at a time when your heart's antioxidant defense mechanism
is critically lowit now becomes overwhelmed.
Remember, in a surgical procedure, any incision exposes your cells to oxygen. Surgery bydefinition generates massive amounts of oxidative stress on your body. Both Japanese and
Canadian researchers have found raising your levels of antioxidant protection prior to
procedures such as angioplasty, coronary bypass and thrombolysis to help prevent
complicationssignificantly improving recovery.
Stroke
You risk having a strokeoften referred to as a "brain attack" because of: Family history Arteriosclerosis High blood pressure High stress Smoking or exposure to second-hand smoke Obesity
Diabetes Low antioxidant mechanism
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Neurologists from the University of California at San Francisco showed the importance of
GSH in protecting the brain from a stroke. They found when GSH levels were low the
result was significantly greater brain damage suffered aftera stroke. Neurosurgeons at the
University of Washington went further, demonstrating that GSH depletion also leads tofurther narrowing of the critical arteries taking oxygen to your brain.
According to a study done by Children's Hospital of Pittsburgh, brain cell levels of
glutathione drop by as much as 80 percent when injured. Specifically of interest, they noted,
Levels of glutathione, - protect brain cells from death when they're deprived of oxygen,
concluding, brain cells die much more quickly when there's a drop in glutathione levels.
Dr. Alan Pressman, in his book 'The GSH PhenomenonNatures Most Powerful Antioxidant
and Healing Agent' sums up, Stroke victims whose glutathione levels are low have a poorer
prognosis than those whose glutathione levels are higher.
As in the case of a heart attack, if you experience a stroke, GSH intervenes to protect and
increase your oddsby minimizing injury to your brain.
Raising GSH Levels
Raising the level of GSH within each cell of your body is a safe method for patients with
heart disease to prevent the recently identified source of disease and inflammationoxidative
free radicals.
As a patient with heart disease, we urge you to investigate the benefits of protecting each cell
in your bodysimply by adding these GSH precursors to you diet.It was found the decline in
GSH levels begins to rapidly occur at age forty in the average population.Clinical studies
have proven that immune depressed individuals have lower GSH concentrations.
The blood and tissues of people with heart disease are marked by critically low GSH levels.
Research trials have revealed a correspondence between low GSH levels and higher
complications.
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2) Coenzyme Q10
Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated
at times to CoQ10, CoQ, Q10, or Q, is a 1,4-benzoquinone, where Q refers to
the quinone chemical group, and 10 refers to the number ofisoprenyl chemical subunits in its
tail.
Biosynthesis
Starting from acetyl-CoA, a multistep
process of mevalonate pathway produces
farnesyl-PP (FPP), the precursor forcholesterol, CoQ, dolichol, and
isoprenylated proteins. An important
enzyme in this pathway is HMG Co-A reductase, which is usually a target for intervention in
cardiovascular complications. The long isoprenoid side-chain of CoQ is synthesized by trans-
prenyltransferase, which condenses FPP with several molecules of isopentenyl-PP (IPP), all
in the trans configuration.[10]
The next step involves condensation of this polyisoprenoid side-
chain with 4-hydroxybenzoate, catalyzed by polyprenyl-4-hydroxy benzoate transferase.
Overview:
Coenzyme Q10 (CoQ10) is a substance that' s found naturally in the body and helps convert
food into energy. CoQ10 is found in almost every cell in the body, and it is a powerful
antioxidant.
Antioxidants fight damaging particles in the body known as free radicals, which damage cell
membranes, tamper with DNA, and even cause cell death. Scientists believe free radicals
contribute to the aging process, as well as a number of health problems, including heart
disease and cancer. Antioxidants, such as CoQ10, can neutralize free radicals and may reduce
or even help prevent some of the damage they cause.
Some researchers believe that CoQ10 may help with heart-related conditions, because it can
improve energy production in cells, prevent blood clot formation, and act as an antioxidant.
Coenzyme Q10
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Coenzyme Q10 in Heart diseases:
Some studies suggest that coenzyme Q10 supplements, either by themselves or in with other
drug therapies, may help prevent or treat the following conditions:
After Heart Attack
One clinical study found that people who took daily CoQ10 supplements within 3 days of a
heart attack were less likely to have subsequent heart attacks and chest pain. They were also
less likely to die of heart disease than those who did not take the supplements. Anyone who
has had a heart attack should talk with their health care provider before taking any herbs or
supplements, including CoQ10.
Heart failure (HF)
There is evidence that CoQ10 may help treat heart failure when combined with conventional
medications. People who have congestive heart failure, where the heart isn' t able to pump
blood as well as it should may also have low levels of CoQ10. Heart failure can cause blood
to pool in parts of the body, such as the lungs and legs. It can also cause shortness of breath.
Several clinical studies suggests that CoQ10 supplements help reduce swelling in the legs;
reduce fluid in the lungs, making breathing easier; and increase exercise capacity in people
with heart failure. But not all studies are positive -- some find no effect -- so using CoQ10 for
heart failure remains controversial. CoQ10 should never be used by itself to treat heart
failure, and you should ask your health care provider before taking it for this condition.
High blood pressure
Several clinical studies involving small numbers of people suggest that CoQ10 may lower
blood pressure. However, it may take 4 - 12 weeks to see any change. In one analysis, after
reviewing 12 clinical studies, researchers concluded that CoQ10 has the potential to lower
systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by 10 mm Hg,
without significant side effects. More research with greater numbers of people is needed.
Don't try to treat high blood pressure by yourself -- see your health care provider for
treatment.
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High cholesterol
People with high cholesterol tend to have lower levels of CoQ10, so CoQ10 has been
proposed as a treatment for high cholesterol, but so far there' s no evidence whether it works
or not. There is some evidence it may reduce side effects from conventional treatment with
cholesterol-lowering drugs called statins, which reduce natural levels of CoQ10 in the body.
Taking CoQ10 supplements can bring levels back to normal. Plus, studies show that CoQ10
may decrease the muscle pain associated with statin treatment. Ask your health care provider
if you are interested in taking CoQ10 with statins.
Diabetes
CoQ10 supplements may improve heart health and blood sugar and help manage high blood
pressure in people with diabetes. Two studies found that 100 mg of CoQ10 twice daily
improved HbA1c levels, a measure of long-term blood sugar control. But another study found
no effect. If you have diabetes, talk to your doctor or registered dietitian before using
CoQ10.
Heart damage caused by chemotherapy
Several clinical studies suggest that CoQ10 may help prevent heart damage caused by certain
chemotherapy drugs, adriamycin, or other athracycline medications. More studies are needed,
however. Talk to your health care provider before taking any herbs or supplements if you are
undergoing chemotherapy.
Heart surgery
Clinical research indicates that introducing CoQ10 prior to heart surgery, including bypass
surgery and heart transplantation, can reduce damage caused by free radicals, strengthen heart
function, and lower the incidence of irregular heart beat (arrhythmias) during the recovery
phase. You shouldn' t take any supplements before surgery unless your health care provider
approves
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3) Alpha-lipoic acid:
Lipoic acid (LA), also known as -lipoic acid[2]
and alpha lipoic acid (ALA) is
an organosulfur compound derived
from octanoic acid. LA contains
twovicinal sulfur atoms (at C6 and C8) attached
by a disulfide bond and is thus considered to be
oxidized (although either sulfur atom can exist
in higher oxidation states). The carbon atom at
C6 is chiral and the molecule exists as two enantiomers R-(+)-lipoic acid (RLA) and S-(-)-
lipoic acid (SLA) and as a racemic mixture R/S-lipoic acid (R/S-LA). Only the R-(+)-
enantiomer exists in nature and is an essential cofactor of four mitochondrial enzyme
complexes. Endogenously synthesized RLA is essential for life and aerobic metabolism.
Biosynthesis and attachment
The precursor to lipoic acid, octanoic acid, is made via fatty acid biosynthesis in the form of
octanoyl-acyl carrier protein. In eukaryotes, a second fatty acid biosynthetic pathway
in mitochondria is used for this purpose.
[5][6]
The octanoate is transfrred from a thioester ofacyl carrier protein to an amide of the lipoyl domain by an octanoyltransferase. The sulfur
centers are inserted into the 6th and 8th carbons of octanoate via the a radical s-adenosyl
methioninemechanism, by lipoyl synthase. The sulfurs are from the lipoyl
synthase polypeptide.[7]
As a result, lipoic acid is synthesized on the lipoyl domain and no
free lipoic acid is produced.
Overview:
Alpha-lipoic acid is an antioxidant that is made by the body and is found in every cell, where
it helps turn glucose into energy. Antioxidants attack "free radicals," waste products created
when the body turns food into energy. Free radicals cause harmful chemical reactions that
can damage cells in the body, making it harder for the body to fight off infections. They also
damage organs and tissues. Other antioxidants work only in water (such as vitamin C) or fatty
tissues (such as vitamin E), but alpha-lipoic acid is both fat- and water-soluble. That means it
can work throughout the body. Antioxidants in the body are used up as they attack free
Lipoic acid
http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-PetersenShay08-1http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-PetersenShay08-1http://en.wikipedia.org/wiki/Organosulfur_compoundhttp://en.wikipedia.org/wiki/Caprylic_acidhttp://en.wikipedia.org/wiki/Vicinal_(chemistry)http://en.wikipedia.org/wiki/Disulfide_bondhttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Enantiomershttp://en.wikipedia.org/wiki/Octanoic_acidhttp://en.wikipedia.org/wiki/Fatty_acid_biosynthesishttp://en.wikipedia.org/wiki/Eukaryoteshttp://en.wikipedia.org/wiki/Mitochondriahttp://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-4http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-4http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-4http://en.wikipedia.org/wiki/S-adenosyl_methioninehttp://en.wikipedia.org/wiki/S-adenosyl_methioninehttp://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-6http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-6http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-6http://en.wikipedia.org/wiki/File:Lipoic-acid-2D-skeletal.pnghttp://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-6http://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/Lipoyl_synthasehttp://en.wikipedia.org/wiki/S-adenosyl_methioninehttp://en.wikipedia.org/wiki/S-adenosyl_methioninehttp://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-4http://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-4http://en.wikipedia.org/wiki/Mitochondriahttp://en.wikipedia.org/wiki/Eukaryoteshttp://en.wikipedia.org/wiki/Fatty_acid_biosynthesishttp://en.wikipedia.org/wiki/Octanoic_acidhttp://en.wikipedia.org/wiki/Enantiomershttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Disulfide_bondhttp://en.wikipedia.org/wiki/Vicinal_(chemistry)http://en.wikipedia.org/wiki/Caprylic_acidhttp://en.wikipedia.org/wiki/Organosulfur_compoundhttp://en.wikipedia.org/wiki/Alpha-lipoic_acid#cite_note-PetersenShay08-1 -
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radicals, but evidence suggests alpha-lipoic acid may help regenerate these other antioxidants
and make them active again.
In the cells of the body, alpha-lipoic acid is changed into dihydrolipoic acid. Alpha-lipoic
acid is not the same as alpha linolenic acid, which is an omega-3 fatty acid that may help
heart health (See also: Alpha linolenic acid.) There is confusion between alpha-lipoic acid
and alpa linolenic acid because both are sometimes abbreviated ALA. Alpha-lipoic acid is
also sometimes called lipoic acid.
Alpha-lipoic acid in Heart diseases:
Diabetes
In several studies, alpha-lipoic acid appears to help lower blood sugar levels. Its ability to kill
free radicals may help people with diabetic peripheral neuropathy, who have pain, burning,
itching, tingling, and numbness in arms and legs from nerve damage.
Alpha-lipoic acid has been used for years to treat peripheral neuropathy in Germany. Most of
the studies that have found it helps have used intravenous (IV) alpha-lipoic acid, however. It'
s not clear whether taking alpha-lipoic acid by mouth will help. Most studies of oral alpha-
lipoic acid have been small and poorly designed. One 2006 study did find that taking alpha-
lipoic acid for diabetic neuropathy reduced symptoms compared to placebo.
Taking alpha-lipoic acid may help another diabetes-related condition called autonomic
neuropathy, which affects the nerves to internal organs. One study found that 73 people with
cardiac autonomic neuropathy, which affects the heart, showed fewer signs of the condition
when taking 800 mg of alpha-lipoic acid orally compared to placebo.
Brain Function and Stroke
Because alpha-lipoic acid can pass easily into the brain, it may help protect the brain and
nerve tissue. Researchers are investigating it as a potential treatment for stroke and other
brain problems involving free radical damage, such as dementia. So far, there' s no evidence
to say whether it works or doesnt.
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II EXOGENOUS ANTIOXIDANTS:
1). Vitamins:
i) Vitamin C (Ascorbic acid)
Vitamin C or L-ascorbic acidor L-ascorbate is an essential nutrient for humans and certain
other animal species. In living organisms ascorbate acts as an antioxidant by protecting the
body against oxidative stress.[1]
It is also a cofactor in at least
eight enzymatic reactions including
several collagensynthesis reactions that, when dysfunctional,
cause the most severe symptoms ofscurvy.[2]In animals
these reactions are especially important in wound-healing
and in preventing bleeding from capillaries.
The vast majority of animals and plants are able to
synthesize their own vitamin C, through a sequence of
four enzyme-driven steps, which convert glucose to vitamin
C.[2]
The glucose needed to produce ascorbate in the liver
(in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a
glycogenolysis-dependent process.[8]
In reptiles and birds the biosynthesis is carried out in
the kidneys.
Overview:
Vitamin C is a water-soluble vitamin, meaning that your body doesn't store it. We have to get
what we need from food, including citrus fruits, broccoli, and tomatoes.
You need vitamin C for the growth and repair of tissues in all parts of your body. It helps the
body make collagen, an important protein used to make skin, cartilage, tendons, ligaments,
and blood vessels. Vitamin C is needed for healing wounds, and for repairing and
maintaining bones and teeth.
Vitamin C is an antioxidant, along with vitamin E, beta-carotene, and many other plant-based
nutrients. Antioxidants block some of the damage caused by free radicals, substances that
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damage DNA. The build-up of free radicals over time may contribute to the aging process
and the development of health conditions such as cancer, heart disease, and arthritis.
It' s rare to be seriously deficient in vitamin C, although evidence suggests that many people
may have low levels of vitamin C. Smoking cigarettes lowers the amount of vitamin C in the
body, so smokers are at a higher risk of deficiency.
Signs of vitamin deficiency include dry and splitting hair; gingivitis (inflammation of the
gums) and bleeding gums; rough, dry, scaly skin; decreased wound-healing rate, easy
bruising; nosebleeds; and a decreased ability to ward off infection. A severe form of vitamin
C deficiency is known as scurvy.
Low levels of vitamin C have been associated with a number of conditions, including high
blood pressure, gallbladder disease, stroke, some cancers, and atherosclerosis, the build-up
plaque in blood vessels that can lead to heart attack and stroke. Getting enough vitamin C
from your diet -- by eating lots of fruit and vegetables -- may help reduce the risk of
developing some of these conditions. There is no conclusive evidence that taking vitamin C
supplements will help or prevent any of these conditions.
Vitamin C plays a role in protecting against various Heart diseases:
Heart Disease
Results of scientific studies on whether vitamin C is helpful for preventing heart attack or
stroke are mixed. Vitamin C doesn't lower cholesterol levels or reduce the overall risk of
heart attack, but evidence suggests that it may help protect arteries against damage.
Some studies -- though not all -- suggest that vitamin C, acting as an antioxidant, can slow
down the progression of atherosclerosis (hardening of the arteries). It helps prevent damage
to LDL ("bad") cholesterol, which then builds up as plaque in the arteries and can cause heart
attack or stroke. Other studies suggest that vitamin C may help keep arteries flexible.
In addition, people who have low levels of vitamin C may be more likely to have a heart
attack, stroke, or peripheral artery disease, all potential results of having atherosclerosis.
Peripheral artery disease is the term used to describe atherosclerosis of the blood vessels to
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the legs. This can lead to pain when walking, known as intermittent claudication. But there is
no evidence that taking vitamin C supplements will help.
The best thing to do is get enough vitamin C through your diet. That way, you also get the
benefit of other antioxidants and nutrients contained in food. If you have low levels of
vitamin C and have trouble getting enough through the foods you eat, ask your doctor about
taking a supplement.
High Blood Pressure
Population based studies (which involve observing large groups of people over time) suggest
that people who eat foods rich in antioxidants, including vitamin C, have a lower risk of high
blood pressure than people who have poorer diets. Eating foods rich in vitamin C is important
for your overall health, especially if you are at risk for high blood pressure. The diet
physicians most frequently recommend for treatment and prevention of high blood pressure,
known as the DASH (Dietary Approaches to Stop Hypertension) diet, includes lots of fruits
and vegetables, which are loaded with antioxidants.
ii) Vitamin E
Vitamin E refers to a group of eight fat-soluble compounds that include
both tocopherols and tocotrienols. There are many different forms of vitamin E, of which-
tocopherol is the most common in the North American diet. -Tocopherol can be found in
corn oil, soybean oil, margarine and
dressings.-Tocopherol, the most
biologically active form of vitamin E, is
the second most common form of vitamin
E in the North American diet. This variant
of vitamin E can be found most abundantly
in wheat germ oil, sunflower, and
safflower oils. It is a fat-
soluble antioxidant that stops the production ofreactive oxygen species formed when fat
undergoes oxidation. As an antioxidant, vitamin E acts as a peroxyl radical scavenger,
preventing the propagation offree radicals in tissues, by reacting with them to form a
tocopheryl radical which will then be oxidizedby a hydrogen donor (such as Vitamin C) and
Vitamin E
The -tocopherol form of vitamin E
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thus return to its reduced state. As it is fat-soluble, it is incorporated into cell membranes,which protects them from oxidative damage.
Overview:
Many claims have been made about vitamin E's potential to promote health and prevent and
treat disease. The mechanisms by which vitamin E might provide this protection include its
function as an antioxidant and its roles in anti-inflammatory processes, inhibition of platelet
aggregation, and immune enhancement.
A primary barrier to characterizing the roles of vitamin E in health is the lack of validated
biomarkers for vitamin E intake and status to help relate intakes to valid predictors of clinical
outcomes. This section focuses on four diseases and disorders in which vitamin E might be
involved: heart disease, cancer, eye disorders, and cognitive decline.
Coronary heart disease
Evidence that vitamin E could help prevent or delay coronary heart disease (CHD) comes
from several sources.In vitro studies have found that the nutrient inhibits oxidation of low-
density lipoprotein (LDL) cholesterol, thought to be a crucial initiating step for
atherosclerosis [6]. Vitamin E might also help prevent the formation of blood clots that could
lead to a heart attack or venous thromboembolism.
Several observational studies have associated lower rates of heart disease with higher vitamin
E intakes. One study of approximately 90,000 nurses found that the incidence of heart disease
was 30% to 40% lower in those with the highest intakes of vitamin E, primarily from
supplements. Among a group of 5,133 Finnish men and women followed for a mean of 14
years, higher vitamin E intakes from food were associated with decreased mortality from
CHD.
However, randomized clinical trials cast doubt on the efficacy of vitamin E supplements to
prevent CHD. For example, the Heart Outcomes Prevention Evaluation (HOPE) study, which
followed almost 10,000 patients at high risk of heart attack or stroke for 4.5 years, found that
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participants taking 400 IU/day of natural vitamin E experienced no fewer cardiovascular
events or hospitalizations for heart failure or chest pain than participants taking a placebo. In
the HOPE-TOO followup study, almost 4,000 of the original participants continued to take
vitamin E or placebo for an additional 2.5 years. HOPE-TOO found that vitamin E providedno significant protection against heart attacks, strokes, unstable angina, or deaths from
cardiovascular disease or other causes after 7 years of treatment. Participants taking vitamin
E, however, were 13% more likely to experience, and 21% more likely to be hospitalized for,
heart failure, a statistically significant but unexpected finding not reported in other large
studies.
The HOPE and HOPE-TOO trials provide compelling evidence that moderately high doses of
vitamin E supplements do not reduce the risk of serious cardiovascular events among men
and women >50 years of age with established heart disease or diabetes. These findings are
supported by evidence from the Women's Angiographic Vitamin and Estrogen study, in
which 423 postmenopausal women with some degree of coronary stenosis took supplements
with 400 IU vitamin E (type not specified) and 500 mg vitamin C twice a day or placebo for
>4 years [22]. Not only did the supplements provide no cardiovascular benefits, but all-cause
mortality was significantly higher in the women taking the supplements.
The latest published clinical trial of vitamin E's effects on the heart and blood vessels of
women included almost 40,000 healthy women 45 years of age who were randomly
assigned to receive either 600 IU of natural vitamin E on alternate days or placebo and who
were followed for an average of 10 years. The investigators found no significant differences
in rates of overall cardiovascular events (combined nonfatal heart attacks, strokes, and
cardiovascular deaths) or all-cause mortality between the groups. However, the study did find
two positive and significant results for women taking vitamin E: they had a 24% reduction in
cardiovascular death rates, and those 65 years of age had a 26% decrease in nonfatal heart
attack and a 49% decrease in cardiovascular death rates.
The most recent published clinical trial of vitamin E and men's cardiovascular health included
*almost 15,000 healthy physicians 50 years of age who were randomly assigned to receive
400 IU synthetic alpha-tocopherol every other day, 500 mg vitamin C daily, both vitamins, or
placebo. During a mean followup period of 8 years, intake of vitamin E (and/or vitamin C)
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had no effect on the incidence of major cardiovascular events, myocardial infarction, stroke,
or cardiovascular morality. Furthermore, use of vitamin E was associated with a significantly
increased risk of hemorrhagic stroke.
In general, clinical trials have not provided evidence that routine use of vitamin E
supplements prevents cardiovascular disease or reduces its morbidity and mortality.
However, participants in these studies have been largely middle-aged or elderly individuals
with demonstrated heart disease or risk factors for heart disease. Some researchers have
suggested that understanding the potential utility of vitamin E in preventing CHD might
require longer studies in younger participants taking higher doses of the supplement.
Further research is needed to determine whether supplemental vitamin E has any protective
value for younger, healthier people at no obvious risk of CHD.
2. Antioxidants Phytochemicals - photosynthetic nutrients/ plant pigments.
i) CAROTENOIDS
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in
the chloroplasts and chromoplasts of plants and
some other photosynthetic organisms like algae,
some bacteria, and some types offungus.
Carotenoids can be synthesized fats and other
basic organic metabolic building blocks by all
these organisms. Carotenoids generally cannot be
manufactured by species in the animal kingdom
(although one species of aphid is known to have
acquired the genes for synthesis of the
carotenoid torulene from fungi by horizontal gene
transfer[1]
). Animals obtain carotenoids in their
diets, and may employ them in various ways in
metabolism. There are over 600 known
carotenoids; they are split into two
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classes, xanthophylls (which contain oxygen) and carotenes (which are purely hydrocarbons,
and contain no oxygen). Carotenoids in general absorb blue light. They serve two key roles in
plants and algae: they absorb light energy for use in photosynthesis, and they protect
chlorophyll from photodamage.
[2]
In humans, four carotenoids (beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin) have vitamin A activity (meaning they
can be converted to retinal), and these and other carotenoids can also act as antioxidants. In
the eye, certain other carotenoids (lutein and zeaxanthin) apparently act directly to absorb
damaging blue and near-ultraviolet light, in order to protect the macula lutea.
Carotenoid in heart diseases:
Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has
a significant role in the prevention of many chronic diseases such as Cardiovascular Diseases,
cancers, and degenerative brain diseases. The major risk and protective factors in the diet are
well recognized, but interesting new candidates continue to appear.
It is well known that a greater intake of fruit and vegetables can help prevent heart diseases
and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is
difficult to pinpoint any single nutrient that contributes the most to the cardioprotective
effects.
Several potential components that are found in fruit, berries, and vegetables are probably
involved in the protective effects against CVD. Potential beneficial substances include
antioxidant vitamins, folate, fiber, and potassium.
Antioxidant compounds found in fruit and vegetables, such as , carotenoids, and flavonoids,
may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this
review, the role of main dietary carotenoids, ie, lycopene, -carotene, -carotene, -
cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed.
Although it is clear that a higher intake of fruit and vegetables can help prevent the
morbidity and mortality associated with heart diseases, more information is needed to
ascertain the association between the intake of single nutrients, such as carotenoids, and the
risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the
treatment or prevention of heart diseases cannot be recommended.
http://en.wikipedia.org/wiki/Xanthophyllhttp://en.wikipedia.org/wiki/Carotenehttp://en.wikipedia.org/wiki/Carotenoid#cite_note-1http://en.wikipedia.org/wiki/Carotenoid#cite_note-1http://en.wikipedia.org/wiki/Carotenoid#cite_note-1http://en.wikipedia.org/wiki/Beta-carotenehttp://en.wikipedia.org/wiki/Alpha-carotenehttp://en.wikipedia.org/wiki/Alpha-carotenehttp://en.wikipedia.org/wiki/Gamma-carotenehttp://en.wikipedia.org/wiki/Cryptoxanthinhttp://en.wikipedia.org/wiki/Vitamin_Ahttp://en.wikipedia.org/wiki/Retinalhttp://en.wikipedia.org/wiki/Antioxidanthttp://en.wikipedia.org/wiki/Luteinhttp://en.wikipedia.org/wiki/Zeaxanthinhttp://en.wikipedia.org/wiki/Macula_luteahttp://en.wikipedia.org/wiki/Macula_luteahttp://en.wikipedia.org/wiki/Zeaxanthinhttp://en.wikipedia.org/wiki/Luteinhttp://en.wikipedia.org/wiki/Antioxidanthttp://en.wikipedia.org/wiki/Retinalhttp://en.wikipedia.org/wiki/Vitamin_Ahttp://en.wikipedia.org/wiki/Cryptoxanthinhttp://en.wikipedia.org/wiki/Gamma-carotenehttp://en.wikipedia.org/wiki/Alpha-carotenehttp://en.wikipedia.org/wiki/Alpha-carotenehttp://en.wikipedia.org/wiki/Beta-carotenehttp://en.wikipedia.org/wiki/Carotenoid#cite_note-1http://en.wikipedia.org/wiki/Carotenehttp://en.wikipedia.org/wiki/Xanthophyll -
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Although carotenoids are not essential for human health, they have biological actions that
may be important in maintaining health and preventing the appearance of serious diseases
such as cancer, pulmonary disorders, and cataract.
Epidemiologic studies have also shown that a high intake of carotenoids is associated with a
reduced risk of CVD, although the results of these studies are somewhat conflicting.
A higher intake of fruit and vegetables can help prevent heart diseases and their associated
mortality. More information is needed to clarify the relation between the intake of single
nutrients, such as carotenoids, and the risk of heart diseases.
Because carotenoids are a complex group of nutrients with different chemical structures and
biological actions and because studies of the health effects of carotenoids are heterogeneous,
it is difficult to undertake a meta-analysis or conduct a detailed systematic review about the
health effects of carotenoids.
Note that all the evidence from clinical trials on the effects of carotenoids on heart diseases is
based only on -carotene. Although there have been null findings for -carotene in these
clinical trials, many observational studies investigating single or total carotenoids have shown
that carotenoids are associated with a reduced risk of heart diseases.
Clinical trials are also warranted to evaluate the antioxidative and other health effects of other
carotenoids, such as lycopene, -carotene, -cryptoxanthin, lutein, and zeaxanthin . Despite a
plausible theory that antioxidants can prevent diseases triggered by oxidative damage, trials
thus far have not substantiated this theory.
At the moment, no reason exists to recommend carotenoids in pharmaceutical form for the
treatment or prevention of CHD. When studying associations between nutrients and diseases,
it is important to include not only traditional risk factors, but also other factors which are a
part of a healthy lifestyle such as exercise and nonsmoking, into the statistical models.
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ii) Bioflavonoids (or) Flavonoids
Flavonoids (or bioflavonoids) (from the Latin word flavus meaning yellow, their colour in
nature), are a class ofplant secondary metabolites.
According to the IUPAC nomenclature, they can be classified into:
Flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure(examples: quercetin, rutin).
Isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone)structure
Neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1, 2-benzopyrone) structure.The three flavonoid classes above are all ketone-containing compounds, and as such, are
flavonoids and flavonols. This class was the first to be termed "bioflavonoids." The terms
flavonoid and bioflavonoid have also been more loosely used to describe non-ketone
polyhydroxy polyphenol compounds which are more specifically termed flavanoids, flavan-
3-ols (or catechins).
Flavonoids lower vascular disease risk
To conduct the study, researchers analyzed the dietary intake of nearly 100,000 older adults
(average age 70 years) from the US and divided them into five groups based on their reported
flavonoid consumption. The
participants were tracked for a
period of seven years and
assessed for associations
between total flavonoid
ingestion, seven specific
flavonoid classes and
development of heart disease or
cardiovascular mortality.
http://en.wikipedia.org/wiki/Flavushttp://en.wikipedia.org/wiki/Yellowhttp://en.wikipedia.org/wiki/Planthttp://en.wikipedia.org/wiki/Secondary_metabolitehttp://en.wikipedia.org/wiki/IUPAChttp://en.wikipedia.org/wiki/Chromonehttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Quercetinhttp://en.wikipedia.org/wiki/Rutinhttp://en.wikipedia.org/wiki/Isoflavonoidhttp://en.wikipedia.org/wiki/Chromonehttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Neoflavonoidshttp://en.wikipedia.org/wiki/Coumarinehttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Ketonehttp://en.wikipedia.org/wiki/Flavan-3-olhttp://en.wikipedia.org/wiki/Flavan-3-olhttp://en.wikipedia.org/wiki/Flavan-3-olhttp://en.wikipedia.org/wiki/Flavan-3-olhttp://en.wikipedia.org/wiki/Ketonehttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Coumarinehttp://en.wikipedia.org/wiki/Neoflavonoidshttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Chromonehttp://en.wikipedia.org/wiki/Isoflavonoidhttp://en.wikipedia.org/wiki/Rutinhttp://en.wikipedia.org/wiki/Quercetinhttp://en.wikipedia.org/wiki/Benzopyranhttp://en.wikipedia.org/wiki/Chromonehttp://en.wikipedia.org/wiki/IUPAChttp://en.wikipedia.org/wiki/Secondary_metabolitehttp://en.wikipedia.org/wiki/Planthttp://en.wikipedia.org/wiki/Yellowhttp://en.wikipedia.org/wiki/Flavus -
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After compiling the data, scientists determined that those individuals with the highest
consumption of flavonoids (top fifth) were eighteen percent less likely to die of heart disease
or stroke compared to those eating the lowest amount of flavonoids. Any intervention that
can lower the risk of either of these chronic and potentially fatal diseases by close to twentypercent should be considered relevant and can make a big difference when considered as part
of a population level analysis.
The lead researcher from the American Cancer Society, Marjorie L. McCullough commented
"Flavonoid-rich foods also contain many other healthful nutrients, so it's hard to know
whether the compounds, themselves, deserve all the credit for the lower cardiovascular
risks."
A wealth of prior studies have found that a diet rich in fresh vegetables and fruits is beneficial
to vascular health, in part due to the myriad of flavonoid compounds and also due to the high
content of B vitamins and other carotenoids known to lower disease risk.
It is important to note that the people in the top fifth of participants consumed 24 servings of
vegetables and 20 servings of fruits each week, demonstrating that large quantities are not
necessary for maximum benefits.
McCullough concluded:
"So even adding one serving of flavonoid-rich food a day could be beneficial".
Although this study did not make specific note of sugar and processed food consumption,
these foods are classified as 'anti-nutrients' and negate the positive benefits of flavonoids and
other plant-based nutrients to lower the risk of heart disease and stroke.
One study evaluated the affect of a plant rich in flavonoids on 120 men and women
diagnosed with high blood pressure and high cholesterol.
The study found significantly decreased systolic and diastolic blood pressure over a 6 month
period linked to the plant flavonoids. Study participants also had reduced total
cholesterol, LDL cholesterol, triglycerides, and increase HDL cholesterol.
More studies are needed, but a there is a definite link between flavonoids and reduced blood
pressure.
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3. Antioxidant Minerals
i) Selenium:
An Essential Mineral, Selenium is a natural antioxidant which delays the oxidation of
polyunsaturated fatty acids and preserves the elasticity of tissue. Selenium is required for the
production of certain prostaglandins which decrease platelet aggregation. In synergy with
vitamin E, selenium promotes normal growth and fertility, and
improves the function of certain energy producing cells. Both
selenium and vitamin E independently stimulate the formation
of antibodies, proteins that act as the body's defense system.
Selenium protects normal cell function by supporting the body'snatural defenses and scavenging harmful free radicals. Daily
intake of Selenium greatly reduce occurrence of some cancers.
Selenium is an essential constituent of a
number of enzymes, some of which have antioxidant functions.
Deficiency of the element in animals makes them susceptible to
injury by certain types of oxidative stress. At least 1 human
disease occurs only in selenium-deficient individuals. Therefore, it seems prudent to avoidselenium deficiency. The plasma (or serum) selenium concentration is often used to assess
selenium nutritional status. A plasma selenium concentration of 8 micrograms/dL or greater
in a healthy subject indicates that plasma selenoproteins are optimized and the subject is
selenium replete.
The Third National Health and Nutrition Examination Survey determined plasma
selenium in 17,630 subjects in the United States. Its results indicate that more than 99% of
the subjects studied were selenium replete.
The Institute of Medicine has set the Recommended Dietary Allowance for selenium
at 55 micrograms per day for adults. Since most estimates of selenium intake in the United
States are 80 micrograms per day or greater, routine selenium supplementation is not
recommended in the United States.
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Selenium and Chronic Heart Failure
Selenium deficiency was identified as a factor in the etiology of heart failure syndromes in
areas of very low selenium intakes, such as China, where an endemic selenium-responsive
cardiomyopathy is called Keshan disease. Similar cases of cardiomyopathy were reported in
HIV-infected patients and in subjects on parenteral nutrition. The patient with Crohns
disease described by Inoko et al falls into the latter category. When the patient developed his
first episode of heart failure, the serum selenium level was not very low (62 mg/L). Low
selenium was unlikely the single cause of heart failure, although it certainly contributed.
Supplementation improved the condition of the patient but did not normalize the left
ventricular dysfunction, and despite selenium supplementation for 11 years, the
echocardiographic findings gradually deteriorated. The patient was free from symptoms of
heart failure for 11 years and died suddenly.
This discrepancy between the symptoms of heart failure and left ventricular dysfunction
emphasizes that the pathophysiology underlying the symptoms of chronic heart failure is
complex and poorly understood. There is no single cause of the main symptoms of heart
failure (dyspnea and muscle fatigue), and treatments that correct the hemodynamics of heart
failure do not reliably increase exercise tolerance or reduce the severity of dyspnea.
The case described by Inoko et al suggests that selenium may have a role in the symptoms of
heart failure rather than in the development of left ventricular dysfunction. Yet, selenium
deficiency is not the only cause of Keshan disease, and it coincides with the clinical severity
rather than the prevalence of the cardiomyopathy as assessed by echocardiography.
Possible causes of Keshan disease are viral infection and nutritional factors (insufficient zinc
or molybdenum, excessive barium or lead). However, when serum selenium levels of
residents of an endemic area were raised to the levels found in nonendemic areas, mortality
from Keshan disease dramatically decreased, but clinically latent cases were still found, and
the echocardiographic prevalence of the disease remained high.
Therefore, selenium deficiency seems to be a predisposing factor rather than a specific cause
of Keshan disease. Finally, although the exact cause of Keshan disease remains unknown,
numerous agents probably work synergistically. Thus, if selenium supplementation did
improve the condition of the patient described by Inoko et al, the primary cause of his
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cardiomyopathy remains unknown. The hypothesis that once fully developed, the left
ventricular dysfunction may be irreversible even after use of selenium supplements is not
supported by either their own case or the relevant literature.
ii) Zinc:
Zinc is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first
element in group 12 of the periodic table. Zinc is, in some respects, chemically similar
to magnesium, because its ion is of similar size and its
only common oxidation state is +2. Zinc is the 24th
most abundant element in the Earth's crust and has five
stable isotopes. The most commonzinc ore is sphalerite (zinc blende), a zinc
sulfide mineral. The largest mineable amounts are found
in Australia, Asia, and the United States. Zinc
production includes froth flotation of the ore, roasting,
and final extra
The ability of zinc to retard oxidative processes has been recognized for many years. In
general, the mechanism of antioxidation can be divided into acute and chronic effects.
Chronic effects involve exposure of an organism to zinc on a long-term basis, resulting in
induction of some other substance that is the ultimate antioxidant, such as the
metallothioneins. Chronic zinc deprivation generally results in increased sensitivity to some
oxidative stress. The acute effects involve two mechanisms: protection of protein sulfhydryls
or reduction ofOH formation from H2O2 through the antagonism of redox-active transition
metals, such as iron and copper. Protection of protein sulfhydryl groups is thought to involve
reduction of sulfhydryl reactivity through one of three mechanisms: (1) direct binding of zinc
to the sulfhydryl, (2) steric hindrance as a result of binding to some other protein site in close
proximity to the sulfhydryl group or (3) a conformational change from binding to some other
site on the protein. Antagonism of redox-active, transition metal-catalyzed, site-specific
reactions has led to the theory that zinc may be capable of reducing cellular injury that might
have a component of site-specific oxidative damage, such as postischemic tissue damage.
Zinc is capable of reducing postischemic injury to a variety of tissues and organs through a
mechanism that might involve the antagonism of copper reactivity. Although the evidence for
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the antioxidant properties of zinc is compelling, the mechanisms are still unclear. Future
research that probes these mechanisms could potentially develop new antioxidant functions
and uses for zinc.
Zinc and cardiovascular disease
The role of antioxidants such as zinc in heart disease is also important. This is again shown in
2 recent studies.
One study suggests that having optimal anti-oxidant levels makes heart stents less likely to
get blocked up. The second study suggests that high iron and copper levels and low zinclevels are associated with an increased risk of heart attacks.
Iron are oxidative (i.e., the
opposite of antioxidants).
The authors conclude, "Deficiency of zinc and high concentration of copper and iron may
play a role in the development of heart disease."
All of these factors are already taken into account in the Energy Revitalization
System vitamin powderwhich can help you stay heart healthy. It is very high in
antioxidants, has an optimal amount of zinc (too much worsens HDL cholesterol), has very
little copper (too little copper is also dangerous, so you want the right balance), and no iron.
The fact that it has an important role in states of cardiovascular diseases has been studied and
described by several research groups. It appears to have protective effects in coronary artery
disease and cardiomyopathy. Intracellular zinc plays a critical role in the redox signaling
pathway, whereby certain triggers such as ischemia and infarction lead to release of zinc from
proteins and cause myocardial damage. In such states, replenishing with zinc has been shown
to improve cardiac function and prevent further damage. Thus, the area of zinc homeostasis is
emerging in cardiovascular disease research. The goal of this report is to review the current
knowledge and suggest further avenues of research.
http://www.endfatigue.com/store/products/supplements/berry-splash/http://www.endfatigue.com/store/products/supplements/berry-splash/http://www.endfatigue.com/store/products/supplements/berry-splash/http://www.endfatigue.com/store/products/supplements/berry-splash/ -
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4) Antioxidant : Harmones
Melatonin
Melatonin, also known chemically asN-acetyl-5-methoxytryptamine, is a naturally
occurring compound found in animals, plants, and microbes. In
animals, circulating levels of the hormone melatonin vary in a
daily cycle, thereby allowing the entrainment of the circadian
rhythms of several biological functions.
Many biological effects of melatonin are produced through
activation ofmelatonin receptors, while others are due to its role
as a pervasive and powerfulantioxidant, with a particular role in
the protection ofnuclear and mitochondrial DNA.
In mammals, Melatonin, produced in the pineal gland which is outside of the blood-brain
barrier, acts as an endocrine hormone since it is released into the blood. Melatonin is
biosynthesized in four enzymatic steps from the essential dietary amino acid tryptophan,
with serotonin produced at the second step. Melatonin is secreted into the blood by the pineal
gland in the brain. Known as the "hormone of darkness", it is secreted in darkness in both
day-active (diurnal) and night-active (nocturnal) animals. It may also be produced by a
variety of peripheral cells such as bone marrow cells, lymphocytes, and epithelial cells.
Beneficial effects of melatonin in cardiovascular disease.
The experimental data obtained from both human and rodent studies suggest that melatonin
may have utility in the treatment of several cardiovascular conditions. In particular,
melatonin's use in reducing the severity of essential hypertension should be more widely
considered. In rodent studies melatonin has been shown to be highly effective in limiting
abnormal cardiac physiology and the loss of critical heart tissue resulting from
ischemia/reperfusion injury. Melatonin may also be useful in reducing cardiac hypertrophy in
some situations and thereby limiting the frequency of heart failure.
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Finally, some conventional drugs currently in use have cardiotoxicity as a side-effect. Based
on studies in rodents, melatonin, due to its multiple anti-oxidative actions, is highly effective
in abrogating drug-mediated damage to the heart. Taken together, the findings from human
and animal studies support the consideration of melatonin as a cardioprotective agent
There has been little research about melatonin's effects on cardiovascular disease, but a recent
study at the Institute for Cardiovascular Diagnosis And Therapy in Salzburg, Austria
produced some eye-opening findings.
They looked at nightly melatonin levels in the serum of two groups of subjects: 2 women and
13 men with documented coronary heart disease (mean age 54) and 2 healthy women and 8
healthy men (mean age 53). They measured serum melatonin levels in these subjects, both in
the afternoon and at night.
Melatonin was not detectable in either group during the afternoon. At night, when melatonin
does its work, however, the results were very different. The scientists found that melatonin
levels in the coronary disease patients was five times lower than in healthy subjects!
They speculated that, since melatonin reduces noradrenaline, which may inflict damage in
arterial walls, the lack of melatonin in individuals with coronary heart disease fails to keep
their noradrenaline levels in check. It would be interesting to determine if individuals who
suffer heart attacks have depleted melatonin levels before their heart attack, or if their
depleted melatonin levels are a consequence of their heart attack.
What's very clear, however, is that replenishing the depleted melatonin levels in coronary
heart disease patients could be a very effective therapy, and that maintaining youthful
melatonin levels could be an effective way of preventing heart attacks, strokes, and
other cardiovascular diseases.
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Conclusions:
Our concept of the relationship between antioxidants and
coronary heart disease has changed considerably over the past 2 decades, in large part
because of the accrual and analysis of large population data sets, the availability of more
detailed food composition information, and, particularly, critical breakthroughs in our
understanding of disease mechanisms. With regard to the latter, considerable evidence now
suggests that oxidants are involved in the development and clinical expression of coronary
heart disease and that antioxidants may contribute to disease resistance. Consistent with this
view is epidemiological evidence indicating that greater antioxidant intake is associated with
lower disease risk. Although this increased antioxidant intake generally has involved
increased consumption of antioxidant-rich foods, some recent observational studies have
suggested the importance of levels of vitamin E intake achievable only by
supplementation. There is currently no such evidence from primary prevention trials, but
results from secondary prevention trials have shown beneficial effects of vitamin E
supplements on some disease end points. In contrast, trials directly addressing the effects of
-carotene supplements have not shown beneficial effects, and some have suggesteddeleterious effects, particularly in high-risk population subgroups.
In view of these findings, the most prudent and scientifically supportable recommendation for
the general population is to consume a balanced diet with emphasis on antioxidant-rich fruits
and vegetables and whole grains. This advice, which is consistent with the current dietary
guidelines of the American Heart Association,42
considers the role of the total diet in
influencing disease risk. Although diet alone may not provide the levels of vitamin E intake
that have been associated with the lowest risk in a few observational studies,19
20
the absence
of efficacy and safety data from randomized trials precludes the establishment of population-
wide recommendations regarding vitamin E supplementation. In the case of secondary
prevention, the results from clinical trials of vitamin E have been encouraging, and if further
studies confirm these findings, consideration of the merits of vitamin E supplementation in
individuals with cardiovascular disease would be warranted.
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