antioxidants: more details, please

Good info on flavonoids. Have fun!

http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf

Jack N Dalton

"Ted Shoemaker" <[email hidden]> wrote in message
news:[email hidden]...

Quoted message said:

Hello,

For the last few years we have been told to take those foods that
contain antioxidants. A few foods have been listed as containing
antioxidants, and the information usually stops there.

Presumably, there is more than one antioxidant. What are the
different kinds? Which foods (and herbs and teas) have which
particular kinds?
What are their different effects?

Please respond to the newsgroup and not to my email.

Thank you very much!

Ted Shoemaker

"jack n dalton" <[email hidden]> wrote in message news:<[email hidden]>...

Quoted message said:

Good info on flavonoids. Have fun!

http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf

Thanks for the link. There's a lot of good stuff in there, and I
haven't read it all yet.

Now for the ignorant question:
What is the relationship between antioxidants and flavonoids?
Are all antioxidants flavonoids?
Are all flavonoids antioxidants? etc.

Please respond to the group, and not to my email.

Thank you!

Ted Shoemaker

"Ted Shoemaker" <[email hidden]> wrote in message
news:[email hidden]...

Quoted message said:

"jack n dalton" <[email hidden]> wrote in message

news:<[email hidden]>...

Quoted message said:

Quoted message said:

Good info on flavonoids. Have fun!

http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf

Thanks for the link. There's a lot of good stuff in there, and I
haven't read it all yet.

Now for the ignorant question:
What is the relationship between antioxidants and flavonoids?
Are all antioxidants flavonoids?
Are all flavonoids antioxidants? etc.

Please respond to the group, and not to my email.

Thank you!

Ted Shoemaker

I believe this should cure your ignorance. So here it is...

Jack N Dalton

Antioxidants

Background

About 21% of the Earth's atmosphere is made up of oxygen. Humans and other
animals have to breathe in oxygen to generate the energy necessary for life
on this planet. But because we have to use oxygen, tissues in our body
become damaged over time through a process called oxidation.
The easiest way to explain oxidation is to simply state that our atmosphere
is known as an oxidizing atmosphere because it contains oxygen and this
atmosphere will oxidize (corrode) metals over time. Iron rusts, while other
metals such as copper, brass, aluminum and silver develop surface deposits
(corrode) when exposed to air. Air can also damage other materials such as
paper, rubber and plastic over a period of time. If we remove the oxygen
from the air, then no damage occurs and many of our important documents,
like the Declaration of Independence, are stored under an atmosphere that is
devoid of oxygen.

Because humans have to use oxygen to live on this planet, we oxidize over
time just like metal, paper, rubber and plastic oxidizes. This oxidation is
often referred to as the aging process. If we had no protection from this
oxidation, we would age extremely quickly. We paint iron to try to keep it
from rusting. In humans and other animals, we use antioxidants to try to
slow this oxidation process down so we can live for a decent period of time.
One factor that appears to determine the maximum life span of an animal is
how good it's antioxidant defense system is.

Oxidizing Agents

Oxygen is the major oxidizing agent that humans have to deal with on a
regular basis in terms of quantity but many other kinds of oxidants can be
formed from oxygen in the human body. While oxygen is bad, these other
oxygen-derived agents are even worse. Scientists use the term free radicals
to refer to these other oxidizing agents that can be formed from oxygen in
the human body. Even scientists have a hard time explaining to each other
what free radicals are and what kinds of damage they can do in the body. The
easiest way to try to explain this concept is to compare oxygen with ozone.
Oxygen, which is O2, can damage human lung tissue but ozone, which is O3,
does much more damage to human lung tissue than does oxygen. This is why the
EPA is trying to limit the amount of ozone in the air that humans breathe by
limiting the pollution that is responsible for ozone formation in our lower
atmosphere. Ozone is so much more reactive than oxygen that it is often used
as an equipment sterilization gas in hospital operating rooms to kill
bacteria by oxidizing them to the point that they can no longer survive.
While ozone does much more oxidative damage than oxygen does, it's not a
free radical.

Oxygen-Derived Free Radicals in Humans

We have identified many of the oxygen-derived free radicals that are formed
in humans. If we know what we have to defend against, then it's easier to
protect ourselves. Very few of you will recognize all of these agents but
that's okay, it's only the concept that's important (there are many bad free
radicals in our body). Before I give you the list of free radicals that we
have to deal with, I want to point out that oxygen does damage too but the
damage that oxygen does is very easy for us to deal with. When oxygen causes
oxidative damage, the damage can be very easily repaired by reducing the
compound in the cell that was damaged by the oxygen.

When oxygen oxidizes something, it generally takes two electrons from the
compound that it's oxidizing so it can form water. This means that to repair
the damage that oxygen did, we have to add those two electrons back to what
was damaged by the oxygen. We have many different agents in our cells that
can do this, things like NADH2, FADH2, NADPH2, glutathione, lipoic acid and
vitamin C. This two-electron damage is very easy to repair. The only problem
would be if the amount of oxidative damage exceeded our repair system's
ability to fix the damage.

While two electron damage is generally very easy to repair, one electron
damage is extremely difficult to repair. Free radicals cause one electron
damage to compounds in our cells. The free radicals known to occur in human
tissues are: 1) nitric oxide, 2) superoxide (O2-), 3) singlet oxygen (O-),
4) peroxynitrite, 5) hypochlorite, 6) hydroxyl free radicals, and 7) peroxyl
free radicals. Once a free radical is formed, it reacts very quickly to
generate additional free radicals. This process of additional free radical
formation is referred to as a chain reaction process, just like what occurs
with radioactive material. To keep nuclear power plants from going critical
(uncontrolled nuclear chain reaction) we have to use control rods or water
to capture some of the material being released by the nuclear fission
process. We do the same thing in the human body by using antioxidants to
capture some of the free radicals that are formed. The key to understand
here is that it's impossible to capture all of the free radicals and even if
we could do it, we would not want to do it because then our immune system
would not work at all.

Our immune system kills infectious agents by purposely producing free
radicals (superoxide, nitric oxide and peroxynitrite). If we had a 100%
effective antioxidant defense system, then no bacteria, parasites, viral
infected cells or cancer cells could be killed in our body. We would not age
but that would be little comfort because we would die very quickly from an
infection.

Reactive Oxygen Species in Humans

In addition to free radicals, there are other agents in our body that can
damage our tissues and make us age. While the oxidative theory of aging is
just one of over 300 different theories that have been proposed to explain
human aging, it is the most widely accepted and reasonable explanation for
why humans and other animals age. There are other theories also that have
been proposed to explain many human illnesses, such as cancer, heart disease
and arthritis, also on the basis of oxidative damage. The unifying theme in
all of these theories is reactive oxygen stress.

Oxygen has three different forms. The most common form is molecular oxygen
(O2), which is the gas that we breathe. There is also elemental oxygen (O)
and ozone (O3). All three forms of oxygen can cause oxidative damage in the
human body. We take molecular oxygen and transfer four electrons to it in
our mitochondria (the cell's power plant) to form 2 molecules of water (H2O)
and generate energy as ATP. Electrons are supposed to move in pairs to
molecular oxygen in our mitochondria but once in awhile, only one unpaired
electron moves to oxygen. When this happens, we generate superoxide (O2-) or
singlet oxygen (O-). If just one single electron goes to molecular oxygen,
we end up with superoxide and if three electrons go to molecular oxygen,
then we end up with one molecule of water and one molecule of singlet
oxygen. Superoxide and singlet oxygen are both free radicals and we produce
them on a constant basis as the cost of using oxygen to give us the energy
we need to live. They damage our mitochondria and we have to replace these
mitochondria on a regular basis and they also leak out of the mitochondria
and damage other parts of the cell, including the DNA in the nucleus.

If molecular oxygen would simply wait for full reduction (all four electrons
transferred to give two molecules of water), then there would be no
superoxide or singlet oxygen free radicals produced. But it does not wait,
especially when it is given a single unpaired electron. Molecular oxygen can
also react with metals in our body to form superoxide (it will take a single
electron from iron and copper to generate superoxide free radicals). The
more iron and copper that we have in our body, the more superoxide free
radicals formed.

For ozone, which is much more reactive than molecular oxygen, it quickly
pulls a single electron from anything it comes in contact with (lipid,
protein, DNA, carbohydrate, etc.). This then generates molecular oxygen (O2)
plus the singlet oxygen free radical (O-). Ozone is said to be a potent free
radical generator. It's this high rate of generation of free radicals that
makes ozone so much worse than molecular oxygen. While molecular oxygen can
and does generate free radicals, it's not as good at doing it as ozone is.
Other free radical generators tat we know of in the human body include
hydrogen peroxide and hypochlorous acid.

Free radical generators and the free radicals themselves, cause what is
commonly called reactive oxygen stress. The role of antioxidants is to
decrease this stress.

The Antioxidant Defense System

Antioxidants can prevent free radical generators from generating free
radicals and they can also remove free radicals once they are formed.
However, one very important fact is that no one antioxidant can handle
everything that is going on inside a human cell. Specific antioxidants only
work with specific free radical generators or specific free radicals. For
example, vitamin C can prevent ozone from generating free radicals and it
can also handle the hydroxyl free radicals but it can't handle the other
kinds of oxidative damage that is occurring on a regular basis in the human
cell. One other important fact is that once an antioxidant takes out a free
radical, it becomes a free radical itself. It must then either wait to be
saved by another antioxidant, self destruct or react with something good in
the cell (like DNA) to generate another free radical. The very best
antioxidants will be fairly stable as free radicals (will not tend to
propagate the free radical chain reaction) and will self-destruct if not
saved by another antioxidant. This new understanding of how antioxidants
work has lead to what is now being called the antioxidant network system.
This network is much more important than the presence of any one single
antioxidant in the cell.

Actually, changing the balance of antioxidants present in the cell may
increase oxidative damage rather than decrease it. Using high dose vitamin C
or high dose beta-carotene as single antioxidant supplements appears to
increase oxidative damage in humans rather than decrease it. Both vitamin C
and the carotenoids (beta-carotene) are part of a very extensive antioxidant
network and altering the balance in this network through high dose
supplementation with just one antioxidant does not appear to be beneficial
and may actually be detrimental.

We have tried high dose single antioxidant supplementation with lab animals
(mice and rats) for many years to try to increase their maximum life span
without much success. If humans are going to use antioxidants as
supplements, then the greatest possible variety as possible will be needed
to have any real impact on the oxidative damage that is constantly occurring
in the human body.

The Animal Antioxidants

Animals have to protect themselves from oxidative damage to survive long
enough to reproduce. They do this by synthesizing a wide variety of
different kinds of antioxidants and antioxidant enzymes. We will look first
at the antioxidant enzyme systems.
Animals produce superoxide dismutase to convert the superoxide free radical
to hydrogen peroxide. Two different forms of this enzyme are produced, one
in the mitochondria and one in the cytoplasm. The mitochondrial enzyme
requires manganese to work so the essential mineral manganese is part of the
antioxidant defense system. The cytoplasmic enzyme requires zinc and copper
to work so the essential minerals zinc and copper are also considered to be
part of the antioxidant defense system.

Hydrogen peroxide is a free radical generator so we want to take it out
before it can generate too many free radicals. An enzyme called glutathione
peroxidase will take hydrogen peroxide and convert it to water. Glutathione
peroxidase requires the essential mineral selenium to work so selenium is
also considered to be part of the antioxidant defense system in animals.
Since these four minerals, manganese, selenium, zinc and copper, are only
needed to enable enzymes produced by the cell to work as part of the
antioxidant defense system, using these minerals in supplement form does not
destroy the balance of the antioxidant defense system, it just makes sure
that all the enzyme that the cell is producing to protect itself from
oxidative damage is going to work.
Antioxidants that animals synthesize include vitamin C (but not humans),
coenzyme Q10, lipoic acid, glutathione, taurine and carnitine. Since humans
can not synthesize vitamin C, we must get vitamin C from our diet so it's
considered an essential vitamin for humans. We synthesize all of the other
antioxidants so we do not need them in our diet. If we eat other animals, we
will get these antioxidants from our diet to add to what our body
synthesizes.

All of these animal synthesized antioxidants are now available as
supplements. If extensive oxidative stress is occurring (like smoking a pack
or more of cigarettes per day), getting these animal antioxidants from
supplements may be beneficial but the important thing to remember is that
they all work as part of a network so taking only one as a supplement
without the others is probably not a good idea.

The Plant Antioxidants

While plants do not use oxygen to generate energy (they use sunlight for
energy production), they do produce oxygen as a by-product of
photosynthesis. Just like animals, plants have to protect plant cells from
the oxidative damage that oxygen does in living tissues that are exposed to
oxygen. Plants have developed enzyme systems just like the animals to handle
oxidative stress. However, these enzyme systems have no role in helping
animals protect their cells from oxidative stress (we can never use an
enzyme produced by a plant or another animal to help us because our
digestive system will destroy the enzyme and make it useless in our body).

While the plant produced antioxidant enzymes can not help us, the
antioxidants that plants synthesize can help protect us from oxidative
stress. The main reason why we want Americans to eat more fruits and
vegetables is to get more of these plant antioxidants into our body. There
are three major classes of antioxidants that plants synthesize. These are 1)
tocopherols (which includes the tocotrienols); 2) carotenoids and 3)
flavonoids (which include the quinones). Plants also synthesize vitamin C,
which most animals don't need but humans do.

To be effective, antioxidants must be able to function in a water
(hydrophilic) environment as well as a membrane (hydrophobic) environment.
However, if the antioxidant is water-soluble, it can only function in the
water environment and if it's fat-soluble, then it can only function in the
membrane environment of a plant or animal cell. Plants use vitamin C and the
flavonoids to protect the water environment of the plant cell and they use
the carotenoids, tocopherols and quinones to protect the membrane
environment of the plant cell.

For animals, all of the antioxidants synthesized, except coenzyme Q10, are
water-soluble so they work only in the water environment of the animal cell.
For an animal to protect its cell membranes, it must eat plants or eat
another animal that eats lots of plants (eat a herbivore). Vitamin E is
considered to be an essential fat-soluble vitamin for humans but if humans
or other animals do not get vitamin E, there is no specific deficiency
disease that develops, the major problem that does develop is that the red
blood cells wear out faster than normal (should last about 120 days) from
oxidative damage to the red blood cell membranes.

This comparison of plant and animal antioxidants tells us that plants are
much more concerned about protecting membranes from oxidative damage than
animals are. Photosynthesis occurs in a membrane system in plants and if
this system is not protected, the plant can not get energy and it dies. In
animals, membranes in the mitochondria produce energy but we do not worry
about protecting these membranes that much because when the mitochondria
wears out from oxidative damage, we replace it. The only fat-soluble
antioxidant that animals synthesize is Coenzyme Q10 and this fat-soluble
antioxidant only works in the membranes of the mitochondria.

Another very important difference between plant and animal antioxidants is
variety. Animals do not synthesize that many different antioxidants and the
main one that animals use, based on concentration in the cell, is
glutathione. This is also true for animals that still synthesize vitamin C.
For plants, there are over 5,000 different carotenoids that plants can form,
over 30,000 different flavonoids and quinones that plants can form and about
15 different tocopherols and tocotrienols that plants can form. Each
different antioxidant is good for only specific types of free radicals or
free radical generators in a specific location (water environment or
membrane environment). Plants tailor make their antioxidants to deal with
different unique oxidative environments. If animals eat a wide variety of
different plants, they can drastically increase their antioxidant defense
system. While plant antioxidants are available in supplement form, we have
only a few of them that we can currently take as supplements. For this
reason, a good diet that has 7-9 servings of different fruits and vegetables
each day will be far superior to the typical American diet to which a few
plant antioxidants have been added in supplement form.

I would like to add that my interest is flavonoids/antioxidants is more than
academic.

I have multiple sclerosis and have found the "right flavinoids" can be a
great help.

Jack N Dalton

1: Biochem Pharmacol 2003 Mar 1;65(5):877-85

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity
relationship study.
Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA,
Dijkstra CD.

Department of Molecular Cell Biology, VU Medical Centre, Van der
Boechorststraat
7, 1081 BT, Amsterdam, The Netherlands.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease
multiple sclerosis. During demyelination, macrophages phagocytose myelin and
secrete inflammatory mediators that worsen the disease. Here, we
investigated whether flavonoids, naturally occurring immunomodulating
compounds, are able to influence myelin phagocytosis by macrophages in
vitro. The flavonoids luteolin, quercetin and fisetin most significantly
decreased the amount of myelin phagocytosed by a macrophage cell line
without affecting its viability. IC(50) values for these compounds ranged
from 20 to 80 microM. The flavonoid structure appeared to be essential for
observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4
positions in combination with a C-2,3 double bond were most effective. The
capacity of the various flavonoids to inhibit phagocytosis correlated well
with their potency as antioxidant, which is in line with the requirement of
reactive oxygen species for the phagocytosis of myelin by macrophages. Our
results implicate that flavonoids may be able to limit the demyelination
process during multiple sclerosis.

PMID: 12628496 [PubMed - in process]