antioxidants: more details, please

Good info on flavonoids. Have fun!

nal.usda.govflav.pdfOpen ↗

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!

nal.usda.govflav.pdfOpen ↗

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!

nal.usda.govflav.pdfOpen ↗

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 that 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]