|Speaking of Radicals: Part III- Antioxidant Protection |
|Interview with © Dr. William Pryor|
as Interviewed By© Richard A. Passwater PhD
Dr. William A. Pryor is the Director and Boyd Professor of the Biodynamics
Institute of Louisiana State University in Baton Rouge and the Biochemistry
Department of the LSU Medical Center in New Orleans. He has published over
500 scientific reports and 25 books. He has served as editor of the leading
journal in the field, Free Radical Biology % Medicine and the book
series Free Radicals in Biology.
Dr. Pryor has been awarded more than 14 national and international medals
and honors. He is the holder of four medals from the American Chemical Society,
and three awards from the National Institutes of Health. Dr. Pryor is the
holder of a MERIT Award from the Heart, Lung and Blood Institute of NIH
for 1986-1996. This award ensures continuous funding for outstanding scientists
without further peer review. Dr. Pryor was one of the first four scientists
awarded this honor.
Dr. Pryor has also received awards for the quality of his teaching. He has
been voted the most popular chemistry professor by Phi Lambda Upsilon, the
chemistry honorary undergraduate fraternity. Dr. Pryor has also was honored
with an award for teaching excellence by LSU in 1969 and was given the Outstanding
Educator of America Award in 1974. Whole Foods readers have seen
his ability to clearly communicate complex ideas why during this series.
Also of special interest to Whole Foods readers is that Dr. Pryor
was the Acting Director of the Pennington Biomedical Research Center during
its formation. His mission statement for the Center said, "To further
research for the improvement of human health and lifespan through the study
of nutrition, and particularly the prevention of heart disease and cancer
through dietary and lifestyle factors."
Let's resume where we left off in Part II and discuss how antioxidants protect
us from free radical damage.
Passwater: Dr Pryor, your clear explanations and analogies of free
radicals and free-radical reactions have been very helpful and very much
appreciated. Now can we draw upon your communication skills to clarify how
our bodies defend against free radicals. Let's start with the basics again.
What are antioxidants?
Pryor: An antioxidant is a material that stops fats (primarily polyunsaturated
fatty acids in lipids) from undergoing autoxidation, a process which we
defined earlier. In general, the antioxidants that are important in the
body are the so-called "chain-stopping" antioxidants. These generally
are phenols that donate a hydrogen atom to a peroxyl radical (converting
it to a lipid hydroperoxide). The phenols then form a phenoxyl radical.
Some phenoxyl radicals (vitamin E, BHT, etc.) are so stable that they do
not take part in the chain-carrying reaction (propagation), which would
require them to abstract a hydrogen from another lipid molecule. Instead,
they live long enough to undergo radical combination reactions, which end
Passwater: Fortunately, due to their catalytic-like nature, only
low concentration of the nutritional antioxidants are required relative
to the oxidizable substrates they protect. Thus, we can get significant
amounts in our daily diet. Also, it would seem important that the antioxidant
nutrient reacts with a free radical much more rapidly than the body components
do. Please elaborate on how antioxidants stop free-radical chain propagation
and why this is important.
Pryor: Antioxidants stop free radical chain reactions by exchanging
a hydrogen atom with a chain-carrying peroxyl radical. When this happens,
the free radical center is transferred to the antioxidant. However, since
the antioxidant radical is stable, it does not enter into chain-carrying
reactions. Since chains produce more "bang for the buck," oxidizing
ten or more lipid molecules for each radical that enters the system, stopping
the chain stops damage from occurring to many lipid molecules.
Passwater: What nutrients are generally considered to be antioxidants?
Pryor: The most important lipid-soluble antioxidant is vitamin E.
Other antioxidant nutrients include vitamin C, which functions mainly as
an electron donor, often serving to re-reduce the vitamin E radical back
to vitamin E itself (see figure 3). In addition, beta-carotene and vitamin
A appear to have antioxidant properties under some circumstances. Bioflavonoids
also have antioxidant properties. Coenzyme Q is a phenol, so it behaves
like vitamin E in many tissues. Lipoic acid and glutathione are sulfur-containing
compounds that can act as hydrogen atom donors, thus behaving somewhat like
Oxidants Antioxidants lose electrons gain electrons (are also called
"oxidizers") (are also called "reducers")
Passwater: I notice that you did mention vitamin A as an antioxidant
nutrient. For twenty-five years I have been writing and lecturing about
my research with "the antioxidant nutrients, vitamins A, C and E, plus
the trace mineral selenium." Lately, lay writers have been writing
about "the antioxidant nutrients beta-carotene, vitamin E and vitamin
C." There has been so much emphasis on the merits of beta-carotene
that some have lost sight that vitamin A is a weak antioxidant. The advantages
of beta-carotene are that it is non-toxic, a better antioxidant than vitamin
A, a singlet oxygen quencher, and it improves gap-junction communication.
Yet when I write to the editors of lay magazines such as the US News
& World Report they "stand behind the fact that vitamin A is
not an antioxidant." What can you tell the writers about vitamin A
and beta-carotene as antioxidants?
Pryor: Vitamin A and beta-carotene appear to have antioxidant properties
in some circumstances. Beta-carotene itself is very strange in that it acts
as an antioxidant only in some systems and not in others; at present, no
one understands why this is true. The mechanisms of action of vitamin A
and beta-carotene, as far as their antioxidant properties are concerned,
are understood very much less well than are the properties of vitamin E.
Passwater: In the 1960s, I noted how important combinations of antioxidants
were and successfully obtained patents on synergistic combinations of antioxidants
to slow the aging process and prevent cancer [see CA:80(21)119314x and CA:77(26)168633x].
It was apparent that the extra protective effect was not due to merely filling
different aqueous and lipid compartments. The patents were based on laboratory
animal results, but at that time I did elucidate the mechanisms involved
in the synergism. Today, this information is known thanks to Drs. Lester
Packer, Al Tappel, Graham Burton, yourself and a few others. What do we
know now about how the antioxidant nutrients work together?
Pryor: There is some evidence that vitamin C protects vitamin E,
probably by re-reducing the vitamin E radical, as I mentioned earlier. In
this sense, vitamin E is like the "shock-troops" that actually
attack the enemy. Vitamin C is like the supply troops that keep the shock
troops supplied (in this case, with reducing equivalents).
In general, all this means that the different reducing agents in the body
"talk to one another" freely, and thus, it is probably important
that all of our pools of reducing agents be maintained. For this reason,
most of us in the field recommend that a person take a variety of antioxidants
(a "cocktail"), not just a single one.
- Vitamin E sacrifices itself to stop the free-radical reaction. A vitamin
E radical is formed which in the absence of adequate amounts of other antioxidants,
will decompose and thus be consumed.
- However, if sufficient vitamin C is present, it can re-cycle the vitamin
E and keep up the defense against more free-radicals. In turn, thiols or
other antioxidant nutrients can recycle the vitamin C so that it is not
consumed. The objective is to permit the thiols to be consumed as they can
be plentiful in the diet, whereas vitamins C and E are not.
- The foundation of a good antioxidant defense begins with thiols (sulfur-containing
compounds) and bioflavonoids. They can be in the diet in gram quantities
whereas vitamin C and vitamin E are present only in milligram quantities.
- We can construct an antioxidant pyramid similar to the food pyramid.
Passwater: Figure 4 is an illustration that you devised to teach
the principle that the consumable antioxidant nutrients should be the thiols
(sulfur-containing compounds) and bioflavonoids, not vitamin C and vitamin
E, which are in short supply in our diet. The antioxidant foundation is
built on the more abundant thiols and bioflavonoids. I've used your pyramid
concept to show this quantity relationship as a suggested dietary antioxidant
intake -- in the same manner as the food intake pyramid.
You have mentioned reducing agents and reduction. Let's clarify those terms
for some of our readers, as I find that there is some confusion in some
people's minds between such terms as reducing agent, antioxidant and free
Most of the elementary biochemical reactions involve either acid-base reactions
or oxidation-reduction reactions. Acid-base reactions involve proton
transfer. An "acid" is a proton donor, while a "base"
is a proton acceptor. A proton, just as an electron, is a fundamental unit
of matter. (Let's ignore smaller bits of matter such as quarks. Chemists
work with larger particles than particle physicists do.) The hydrogen atom
consists of a proton and an electron. The hydrogen ion (H+) is
a proton, and vice versa. Thus, saying that an acid is a hydrogen ion donor
is just as correct as saying that an acid is a proton donor.
The second class of reactions often occurring in biochemical reactions is
the oxidation-reduction class. During "oxidation" the chemical
entity of interest losses an electron and increases in oxidation state.
In the case of atoms, an increase in oxidation state is the same as an increase
in valence, however, in the case of molecules, it is more complex than that
as it involves the nature of the chemical bonding and the assignment of
electrons to the atoms involved before and after the reaction. An Oxidizing
agent (electron acceptor) is a reactant that accepts an electron from another
During "reduction" the chemical entity of interest gains an electron
and its oxidation state is decreased. A reducing agent (electron donor)
is a reactant that donates an electron to another reactant.
A "redox" reaction is a reaction in which one or more electrons
are transferred. Thus, acid-base reactions involve proton transfer, while
redox reactions involve electron transfer.
As we discussed in Part II, when molecular oxygen goes to oxygen ions, it
has gained electrons and is said to be reduced. When ferrous iron (Fe+2)
is converted to ferric iron (Fe+3), it has lost an electron and
is said to be oxidized.
The confusion that I often see, is that some treat oxidation reactions and
free-radical reactions as being the same. Would you comment on this, please?
Pryor: Not all free-radical reactions are oxidation reactions and
not all oxidation reactions are free-radical reactions. Some antioxidant
nutrients can play a role as a reducing agent without necessarily behaving
either as an antioxidant or a free-radical scavenger. An example of this
is the inhibitory effect of vitamin C against stomach cancer. This inhibitory
effect is most likely due to ascorbate trapping a nitrosating agent derived
from nitrite and preventing the nitrosation of amines to nitrosamines. In
this reaction, vitamin C acts as a reducing agent by becoming sacrificially
nitrosated, but radicals are not involved. Similarly, beta-carotene may
or may not possess antioxidant and/or free-radical scavenging properties
in systems in which it acts as an anticarcinogenic compound.
Passwater: Do we get an optimal amount of antioxidant nutrients in
our diets? Should the RDAs be set higher to take into consideration heart
disease and cancer risk?
Pryor: I believe that most Americans do not get sufficient antioxidant
nutrients from their diet. Vitamin E is a particularly interesting case,
since the foods that contain it in general are fatty and high in calories,
such as salad dressing, nuts, mayonnaise, etc. The amount of vitamin E that
most of us believe is the minimum necessary for health benefits, 100 IU,
must be obtained from supplements.
Passwater: How strong do you feel that the evidence is that antioxidant
nutrients may reduce the incidence of heart disease and cancer?
Pryor: The evidence that vitamin E reduces heart disease is now quite
strong. Two papers published back-to-back in the New England Journal
of Medicine last year from the group at Harvard that is running the
U. S. Physicians, U. S. Nurses, and Allied Health Professionals studies
published very strong evidence. Their data suggest that heart disease is
cut almost in half for persons who take at least 100 IU of vitamin E per
day for at least two years.
Passwater: And as time goes by, we will continue to get more data
from those studies and even clinical intervention trials. However, researchers
don't pay much attention to data until they can understand the mechanisms
involved. This is where you have been so helpful, and also helpful to our
readers. Thank you.
All rights, including electronic and print media, to this article are copyrighted
to © Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).
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Richard A. Passwater, Ph.D. has been a research biochemist since 1959. His first areas of research was in the development of pharmaceuticals and analytical chemistry. His laboratory......more