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ANTIOXIDANTS

© Copyright 2011 Ty Parr, Ph.D.(All Rights Reserved)  Updated  30Apr2011

What are Free Radicals?       Why Dangerous?     Origins?

Free radicals are molecules with an unpaired electron that are unstable and can react with and damage other important biological molecules in our bodies. The fundamental unit of matter “atoms” that are linked together by chemical bonds make up molecules. Atoms are made of positively charged heavier units called protons and similar heavy but uncharged units called neutrons and finally have a very light (1/1875 of proton mass) negatively charged particle called an electron. The heavy units lie in the center of the atom and the negative electrons swirl around this center. When atoms are linked together in covalent bonds, they share a pair of electrons. Molecules are most stable when electrons are paired in bonds or orbitals (how a stable electron pair is organized around the central nuclei of an atom or shared between atoms in a molecules). Free radicals always involve a molecule (or atom) that is unstable because it has one unpaired electron and is thus able to injure another molecule by stealing one of its electrons that generates a “new free radical victim molecule”. Some 2% of the oxygen we breath is turned into the superoxide radical, a free radical generated in our mitochondria from burning fuel (food). This burning of food for energy takes place in a intra-cellular organelle called the Mitochondria. Mitochondrial metabolism uses som 95% of all the oxygen we breathe in. Mitochondrial metabolism to produce energy from various foods like glucose, fats, and protein residues occurs by a controlled hand off of  electrons through a series of metabolic steps that end in consuming O2 (molecular oxygen) and forming CO2 (carbon dioxide) and water. Free radicals can be created from several of these hand off steps. This starts a chain of potentially dangerous secondary free radical creation. Additionally we can get the formation of free Radicals from some very unstable molecules that can react with simple substances in our body (unbound iron Fe+2 for example) that can then be transformed into free radicals. When talking about this general class of potentially damaging molecules, we often call them ROS (Reactive Oxygen Species) which include both free radicals and these unstable molecules like hydrogen peroxide (H2O2) that can break down into free radicals).

Some free radicals are much weaker that others. Some do not have the chemical strength to remove an electron from most biologically important chemical structures within our cells. A subclass of these weaker free radicals is the "oxidized" or damaged antioxidant molecules that easily "gave up" an electron to a more energetic (biologically dangerous) metabolic produced free radical in search of an electron. This ends the danger from that highly energetic metabolic produced free radical but leaves the weaker antioxidant as a weak free radical themselves. Our body then donates an electron from other metabolic processes to restore the unoxidized antioxidant and the cycle of protection begins again. This process is occurring  on a very large number scale in our cells and prevents destruction of biologically important molecular structures like proteins, nucleic acids (RNA & DNA) and  a variety of other biologically important molecules. Some antioxidants are a “one timesacrificial target that takes the “hit” so that the cell does not have high levels of oxidative damage from these free radicals, but most are rechargeable.

Most of the dangerous free radicals are generated by our energy production process. The major cellular producer of our useful energy  (ATP adenosine triphosphate) is an organelle with our cells called the Mitochondria. The Mitochondria is what is left from the long ago capture of a bacteria by ancient cells that evolved into what we call eucaryotic animal life (all cells that have enclosed nucleus for DNA storage and mitochondria as an energy producing machine inside that cell). Eucaryotes have basically enslaved and changed a bacteria inside our cell as an energy producing machine. Eucaryotic plants  also have captured mitochondria as well as captured light harvesting organelles(themselves left over remains of captured photosynthetic bacteria) to produce carbohydrate, O2 and ATP. Most free radicals (absent pathology) are generated during this energy capture ATP generating process. A lesser amount of free radicals are generated by other cellular processes. In certain disease states, free radicals are produce by the disease at high levels and are responsible for many of the damaging effects we see from those diseases (e.g.. Type 2 or adult onset Diabetes).

Over the length of our life span, there is a slow gradual increase in the prevalence of these damaging free radical molecules. This increase leads to damage to important biological molecules with higher damage later in life.  A young man has some 10% of his cellular protein oxidatively damaged in this free radical process, but a 70 year old man has about 50% of his cellular proteins damaged (Levine, RL & Stadtman, ER  IN: Handbook of the Biology of Aging (4th Ed.) 184-197 (1996)). This is a failure of the process of AUTOPHAGY (breaking down or catabolism of  damaged molecules) described in HOW & WHY? Section that we attributed to elevated TOR gene levels and an absence of sufficient fasting period to activate AUTOPHAGY. The underlying cause of the damage to these proteins is free radical attack. From the 1950’s this gradual increase in free racial creation and consequent damage was believed to be ”the predominant” (but not only) gradual aging process that was principally responsible for our aging and death. 

Because lipids are a major component of living organisms and probably the first easy target of free radicals once they are produced, lipid peroxidation might play an important role in initiating and/or mediating some aspects of the aging process. It has been widely demonstrated that there is an age-associated increase in the steady-state concentrations of lipid peroxidation products. Lipid peroxidation and the aging process.  Praticò D.  Sci Aging Knowledge Environ. 2002 Dec 18;2002(50):re5.   http://www.ncbi.nlm.nih.gov/pubmed/14603026 .

As you can see from the above graph, membrane lipids under go a gradual elevation of free radical damage over the life time that impairs their cellular function. Membrane lipids are of particular concern because these damaging events can have a single free radical molecule onset and go on to have many to 10’s of damaged membrane lipids. This process of amplified or free radical “chain” reaction as a cyclical processes that can generate a huge increase in the levels of oxidatively damaged biologically important unsaturated membrane lipid molecules. This can also spread further free radical damage to other areas of the cell. Our unsaturated membrane lipids are particularly prone to this radical chain reaction. Our body is always repairing the “on going”  damage.

• Free Radical + UnsatMembraneLipid(R) -> (stable former FR) +  •R (damaged membrane lipid as free radical)

• R + R -> Damaged R + •R

repeat last step many to tens of times- get a chain reaction

Similar, but usually less extensive cyclical processes can also occur in the water soluble material of the cell. Many other free radical damages are much more limited to a single target (rather than a chain reaction). If a free radical damages a protein in your cell by a process of adding an oxygen where it does not belong (for  non-sulfur amino acids in a protein), your cell must retire (break into amino acids for re-synthesis) that protein and build it again.  This is a relatively  expensive process energetically.

If a free radical was to damage DNA (our master cellular information source for creating various proteins), we could  suffer a permanent change in the coding information that was “hit”. These DNA mutations are not always fixable, despite a very strong effort of our cells to repair damage. What is pleasing to know is that our nuclear genes (the central cellular DNA warehouse inside a protected organelle called the nucleus) are relatively protected against much damage over most of our life time. Only very late in life does the rate of this “nuclear” DNA damage greatly increase. This remarkable preservation of our nuclear DNA is seen in the various cloning experiments (e.g.. Dolly the sheep) where an adult nucleus (DNA) was placed in an enucleated oocyte (DNA nucleus removed) and then implanted in another sheep for embryonic development to a viable live birth. Dolly the genetically identical off spring was viable and lived most of the duration of a normal sheep’s life. This is in spite of some 90 cell doublings in this process of going from a single cell to the whole adult sheep.

In animal cells,much of the total cellular free radical creation process occurs in the energy producing intracellular organelle called the mitochondria. This mitochondria produces most of our available cellular energy. In the mitochondria, metabolism of various food related glucose, fats, protein residues occurs by a controlled complex stepwise process where food is stripped of chemical energy and then combine with O2 to form CO2 and water. In the process of gaining this energy, some free radicals are created in the mitochondria. These free radicals are at highest concentration inside the mitochondria, The mitochondria also has a small residual “bacterial strand of necessary DNA” encoding genes needed to produce the high amounts of ATP energy. that our cells need. There is a low level of damage to this “bacterial strand of necessary DNA” for most of our life time that very slowly increases until it massively increases in late human life. This is well before any such major increase in damage in our nuclear DNA. Part of the reason for this is the lesser enzymatic repair in the mitochondria and part is due the absence of sufficient AUTOPHAGY to retire old defective (poor energy producing) mitochondria. We covered AUTOPHAGY in the HOW AND WHY section with respect to protein. This lack of AUTOPHAGY of defective (poor energy producing) mitochondria is also a consequence of elevated TOR gene levels. Unfortunately, the mitochondria has much less protection than our central nucleus DNA storehouse, so it accumulates more permanent  radical damage and deletions than the DNA in our nucleus. Eventually, a larger and larger fraction of our mitochondria are not good energy producers and the burden is on the remaining functional mitochondria. Below is a chart of the occurrence of DNA damage to mitochnondrial DNA over the human life span. One obvious solution to this is the use of the compounds DMAE (dimethylaminoethanol) or  Centrophenoxine (a drug containing DMAE that easily gets in to the brain). These will be covered in the SUPPLEMENTS section.

Attempts to gain a longer life span by boosting protection against this slowly rising free radical damage process were done by adding to the diet EXOGENOUS (not produced in the body) antioxidants. These attempts have largely been failures. This was tried by adding natural antioxidants like Vitamins C, E, and a group of plant compounds  called carotenoids (red to yellow colored plant pigments that intercept specific types of free radicals). After this failure, far stronger EXOGENOUS antioxidants were tried in the same process with the similar results. What was gained by these high antioxidant experiments was a realization that many of the diseases of aging were pushed further out in  time, but life spans were not  increased. We need to get enough antioxidants to prevent needless damage and also to put off as much as possible needless diseases of age. As we will learn later in the LONGEVITY section , the combination of antioxidants and natural anti-inflammatories is a much better approach.

After many years of attempting to extend life by one or another EXOGENOUS (not made by the body) antioxidants, genetic recombinant techniques were use to produce fruit flies (http://www.ncbi.nlm.nih.gov/pubmed/8108730) that carried extra copies of ENDOGENOUS antioxidants (Superoxide dismutase that destroys the superoxide radical to form hydrogen peroxide (H2O2) and Catalyase that destroys the H2O2). This worked, extending life  span of this group of relatively short lived flies by 1/3 but in subsequent tests ( http://www.ncbi.nlm.nih.gov/pubmed/12743125 ) did not extend the life span of long lived fly varients. It is clear that life span extension is not much taking place from manipulating antioxidant levels. This does not preclude the postponement of age related diseases but sets the overall tone that antioxidants by themselves are for the most robust health you can gain within the maximum life span we have recorded. We will have to gain additional life span by alternative means that are discussed in LONGEVITY section PDF for SUBSCRIBERS.

Why don't we get rid of these free radicals with some massive level of antioxidants?

Free radicals can not be dispensed with as they are also used as vital signal events for other necessary biologic functions. Thus, we must have these for signal purposes (literally tell our cells what status of oxidant levels) are which is required for a dynamic (changing) homeostasis (stability of overall cell healthy status despite ongoing changes). These metabolically created free radicals modulate other activities and protective responses that generally keeps the whole system in a good healthy  dynamic equilibrium. The levels of free radicals we are talking about is usually well below the elevated levels that cause increases in diseases. Dangers arise when unusual conditions or pathology allow too great a level of free radicals that can have profoundly damaging effects on our cells and tissues. This need not come only from normal metabolism of food, but can also arise from contamination with pathogenic microbes and viruses, drugs, poisons, and even normal molecules in some foods as well as the general assault of a very wide range of industrial and commercial compounds we are exposed to.  Our bodies have multiple redundant systems to try to control and contain these dangerous free radicals, as they are so dangerous to our continued health. We will return to this problem in the SUBSCRIBER ONLY section on LONGEVITY. 

One aspect of these control systems using free radical levels as signal systems is a large number of tyrosine kinase and other kinase systems (kinases & phosphatases respectively transfer or remove phosphates) that modulate cellular activities to maintain homeostasis and enable decisions about cellular activities. Many of these control systems are modulated by free radical oxidation of sulfur containing amino acids (the amino acids Cysteine and cystine as well as the background glutathione system we will discuss shortly). These are the only free radical damage to proteins that can easily be repaired. The oxidized sulfur (R-S-H oxidized to -S=O or R-SO2 or R-SO3 can be reduced back to R-S-H and the protein control molecules restored to functional status. Oxidative changes to non-sulfur  amino acids cannot be repaired but the whole protein must be  broken down to the constituent amino acids and built anew.

Given the need for some free radical activity (as cellular control mechanisms, what we need to do is moderate any elevations of free radicals to more dangerous levels. An even better formulation would be to minimize the most dangerous free radicals that can do irreparable damage to our DNA or other critical cellular molecules. For this we need to know a little about what free radicals are and which are the most dangerous players - so we can block those in particular. This will allow us to focus on what we need to do.

Different Types of Free Radicals

We usually write structures of the free radical molecules with a () character to indicate an unpaired electron. 

THE NEXT TWO FREE RADICAL/ROS  ARE NORMAL PRODUCTS OF METABOLISM AND ARE INFORMATIVE FOR A VARIETY OF SENSITIVE SULFUR BASED KINASE CASCADES THAT ACT TO CONTROL RADICAL LEVELS - BOTH OF THESE HAVE ENDOGENOUS ENZYMES THAT CAN DESTROY THE RADICAL / ROS

Superoxide radical (O2-) a normal side product product of energy metabolism in the mitochondria) used by the body to sense levels of oxidant activity that reacts with sulfur groups of control molecules - can break DNA Stands only by reacting to form another type of free radical OH

Hydrogen peroxide (H2O2 or H-O-O-H) not directly a free radical (but a member of ROS ( Reactive Oxygen Species) but easily breaks into such when it reacts with metal ions like iron (Fe++) to produce hydroxyl radicals - that then can break DNA strands.

THE FOLLOWING FOUR FREE RADICALS ARE THE REAL DANGEROUS BAD BOYS OF FREE RADICALS - THEY CAN ROUTINELY BREAK DNA STRANDS AND CAUSE MUTATIONS. NONE OF THESE BAD BOY RADICALS HAVE ENZYMES THAT DESTROY THEM, THEY NEED TO BE INTERCEPTED BY AN ABUNDANT SUPPLY OF SMALL MOLECULES THAT CAN DETOXIFY THEM. (Gutathione, VItamin C,E, Carotenoids, Melatonin, Flavonoids, Eugenol, etc.).

Hydroxyl radicals ( OH ) , short half-life but very dangerously reactive to wide range of biological molecules - especially including DNA, much of permanent damage is caused by this very reactive but very short lived  radical ,  To block this dangerous radical we need a large number of sacrificial antioxidants in the cell that can take the “hit” and  are such a weak free radical there after that they are just recharged or destroyed by normal cell mechanisms - can break DNA Strands only by generating OH . While extremely energetic and able to attack almost any organic molecule, the extremely short life span of this radical (10-9 seconds) makes it incapable of diffusing far from it’s generation. 

The hydroxyl radical, OH·, is the neutral form of the hydroxide ion (OH­). Hydroxyl radicals are highly reactive and consequently short-lived. The hydroxyl radical has a very short in vivo < in living organism > half-life of approximately (10)-9 second and a high reactivity.[1]. This makes it a very dangerous compound to the organism. Unlike superoxide, which can be detoxified by superoxide dismutase, the hydroxyl radical cannot be eliminated by an enzymatic reaction. It can damage virtually all types of macromolecules: carbohydrates, nucleic acids (mutations), lipids (lipid peroxidation) and amino acids (e.g. conversion of Phe to m-Tyrosine and o-Tyrosine). The only means to protect important cellular structures is the use of antioxidants such as glutathione < or carotenoids, eugenol, etc. > and of effective repair systems.  Hydroxyl radical http://en.wikipedia.org/wiki/Hydroxyl_radical

Singlet oxygen (1O2 ) - a uncharged oxygen molecule that has undergone a promotion of two  electrons from a lower energy triplet state in to different antibonding orbitals of higher energy where both electrons still have the opposite spins. This is usually due to UV-A sunlight exposure as well as metabolic creation via metal ion cyclic oxidation,  A whole broad class of important endogenous & exogenous molecules can quench this dangerous reactive “singlet” state (react with and render harmless: carotenoids, melatonin, glutathione, a-Lipoic Acid, falvonoids, Vitamin C )  Singlet oxygen can  directly break DNA Strands and virtually any other important biological molecule. Produced not only by UVA light but also by cyclic Fe or Cu oxidation of Ascorbic acid (Vitamin C). Many metals (like Fe, Cu, etc.) can cause cyclic singlet production when abundant Vitamin C (or many other antioxidants) are  present.

O2 + UVA -> 1O22 (singlet oxygen)     

Ascorbic acid + Cu+ or Fe++, etc  + O2 -> oxidized Ascorbate + 1O2  (singlet oxygen) + Cu++

Ascorbic acid + Cu++ -> oxidized ascorbate + Cu+

Repeat the last two steps in a cycle and you get a horrific cyclical chain reaction producing many 1O2

Singlet oxygen is the common name used for the diamagnetic form of molecular oxygen (O2), which is less stable than the normal triplet oxygen. Because of its unusual properties, singlet oxygen can persist for over an hour at room temperature, depending on the environment...  One of the roles of carotenoids in photosynthetic systems is to prevent damage caused by produced singlet oxygen by either removing excess light energy from chlorophyll molecules or quenching the singlet oxygen molecules directly... In mammalian biology, singlet oxygen is a form of reactive oxygen species, which is linked to oxidation of LDL cholesterol and resultant cardiovascular effects < heart disease by arterial plaques >. Polyphenol antioxidants can scavenge and reduce concentrations of reactive oxygen species and may prevent such deleterious oxidative effects.[3]  Singlet oxygen  http://en.wikipedia.org/wiki/Singlet_oxygen   

Peroxyradicals  HO-O•   and organic group R form R-COOO•  or can be R-C-O-O• and RC=C(OO•) -R with a unsaturated site in a polyunsaturated fatty acid. These are often created by a prior hydroxyl radical attack on a double bond carbon in an unsaturated fatty acid that then interacts with molecular oxygen to form a peroxyradical that carries the chain reaction forward.  These radicals are extremely dangerous because they are less immediately reactive, have a very long radical half life of 1 second and have a proclivity to attack DNA (thymidine base) and other nucleic acids (RNA). This radical can remove the Thymidine base altogether or even break the DNA strand at the sugar chain. This makes this free radical a real problem needing immediate clean up by small antioxidant molecules.

Peryoxynitrile radicals (O-N-O-O-) (and the series that leads to it : NO2 oxidized from NO  from the original non-free radical  NO (nitric oxide) - NO is a normal required signaling messenger that is required for modulation of blood flow by relaxing the muscles around capillaries ( this includes having  erections in males and  the increased  blood flow during sexual excitement in women ) . NO has many other functions.

NO + O2 (superoxide) -> NO3- (Peryoxynitrile radical).

Peroxynitrite (sometimes called peroxonitrile) is the anion with the formula ONOO-. It is an unstable structural isomer of nitrate, NO3-, which has the same formula but a different structure...  Peroxynitrite is an oxidant and nitrating agent. Because of its oxidizing properties, peroxynitrite can damage a wide array of molecules in cells, including DNA and proteins. Peroxynitrite  http://en.wikipedia.org/wiki/Peroxynitrite

Antioxidant Protection Requires Balanced Fat vs Water Acting Antioxidants

Our own body produces enzyme systems like "superoxide dismutase" (that converts the superoxide radical (•O2-) to H2O2) and "catalyase" that destroys hydrogen peroxide (H2O2) to water an oxygen. Some protection is also conferred by small molecules we synthesize in our own bodies that can accept the unpaired electron and be discarded or regenerated. GLUTHATHIONE is also a critical molecule for our cellular protection that we will shortly learn how to boost.

Plant food is the primary source of EXOGENOUS antioxidants we must get from our foods. Vitamin C and Vitamin E as well as a huge number of plant sourced flavonoids, Proanthocyanidins, and like molecules. These are part of the reason vegetables (especially)  and to a lesser degree fruits were a larger fraction in the Modified Food Pyramid. Most mammals other than humans and hamsters (guinea pigs) can make their own Vitamin C and massively increase production of this during infections and such. We humans can’t make Vitamin C or E nor various carotenoids and flavonols and must get them from our diet and supplements.

A shifting dynamic equilibrium is maintained between our own bodies production of ENDOGENOUS antioxidant enzymes and the levels of intake of EXOGENOUS plant (and supplement) sourced antioxidants, but both are required. By eating a higher amount of protective antioxidants from plants (and supplements), we can bias this system in our favor - especially if we know how totrickour body to produce more ENDOGENOUS antioxidants through exercise and the “trick” of how to boost our GLUTATHIONE levels. Then eating a diet rich in plant foods that have high levels of flavonoids, carotenes, and various vitamins and cofactors greatly augment our protection which can be augmented further by SUPPLEMENTAL antioxidants (covered in the SUPPLEMENTS section).  Do not imagine that you can very well protect yourself by JUST TAKING SUPPLEMENTAL ANTIOXIDANTS, there is just too much NEEDED benefit in fresh vegetables and fruits.

The group of rechargeable plant sourced antioxidants like Vitamin C and Vitamin E are able to be reloaded for many cycles of protective antioxidant action but may be lost by damage or filtration out of the blood into the urine. Some other plant base antioxidants like carotenes also have the ability to be restored to active form and repeat protective action. Many other groups of plant derived antioxidants are basically “sacrificial targets” that perform protection by donating one of their elections to a dangerous unpaired free radical and thus become a very weak free radical that will not be recharged - merely discarded in performing this protection. This means we must replace them regularly by our diet. Below is a graphic chart of the molecular structures of ENDOGENOUS and EXOGENOUS types of antioxidants.

We can categorize our total antioxidant protections as ENDOGENOUS (made by our body)  and EXOGENOUS (from diet or supplements). We will use the RED color to designate ENDOGENOUS and GREEN color for EXOGENOUS to clarify some of the consequences of these two groups and then DEMONSTRATE HOW WE CAN HAVE THE BEST OF BOTH BY A FEW SIMPLE TECHNIQUES. You simply will not find this from other Internet information sources.

STRUCTURES OF ANTIOXIDANTS

.......ENDOGENOUS.............PLANT OR MICROBE  DERIVED   ENDOGENOUS ANTIOXIDANTS

...................................................POLYHYDROXYLIC.........CAROTENES & Vitamins C & E

Click ENDOGENOUS..........Click POLYPHENOLICS.....Click CAROTENES..Click VITAMIN C & E.

Table - antioxidants and what types of free radicals they can handle

(refer to the above graphic to see molecular structure)

 

TYPE

Aqueous

Lipid

both

Superoxide

•O2-

Peroxide

H202

Hydroxy radical

•OH

Singlet Oxygen

1O2

Peroxyradical

R-O-O•

Peroxinitrite

(all NO types )

ONOO-• NO2• .NO

(ENDOGENOUS)              
Superoxide dismutase
Aqueous
O2-
NO2
Catalyase
Aqueous
 
H202
       
Glutathione
Aqueous
 
•OH
1O2
NO2•/ONOO-•
a-Lipoic Acid
both
 
OH• & HClO
1O2
ROO•
 NO2•/ONOO-•
Melatonin
both
 
H202
OH•
1O2
ROO•
NO2•/ONOO-•
(EXOGENOUS)
 
Vitamin C
Aqueous
 
•OH
1O2
NO2•/ONOO-•
Carotenes
Lipid
 
1O2
R-O-O•
NO2•/ONOO-•
Flavonoids &Proanthocyanins
Aqueous
 
•OH
Vitamin E
Lipid
 
•OH
R-O-O•
Eugenol
both
 
•OH
1O2
R-O-O•
NO2•/ONOO-•
a-D-Limonene
Lipid
 

 

Detailed Information on Types of ANTIOXIDANTS

ENDOGENOUS

Superoxide Dismutase (SOD) -  The sole function of this molecule is to destroy superoxide  O2- . Different molecular molecules of SOD are present in the cytoplasm (Cu SOD Copper based SOD) and a different longer lived mitochondrial type (MnSOD, manganese based SOD). Without this in sufficient levels we would die.

Catalyase - Sole function of catalyase is to react with hydrogen peroxide (H2O2) to release the near harmless  O2 and H20. Half life of catalyase depends upon the tissue it is expressed in. Without this in sufficient levels we would die.

Glutathione - One of the most important endogenous protections we have. For example, very little vitamin C gets in to the brain, most of the protection of our brain tissue is by glutathione. Humans have a very wide range of glutathione levels because of differences in intake of sulfur amino acids (cysteine and cystine that comprise the limiting sources). Health is best served by having high levels of glutathione (in high range for humans ). This is the central molecule to recharge our other antioxidants. Without this in sufficient levels we would die.

a-Lipoic Acid - A disulfide (S-S) cyclic ring that is reduced in our cells to the (-S-H sulfhydryl) form. Without this in sufficient levels we would die. 

Melatonin - Called the Dark hormone as it is only produced during periods of darkness (light inhibits its production during the day and light at night will destroys already produced levels in the dark or supplement taken just before sleep). Powerful antioxidant with an elimination half life @ 48 minutes in the blood (release spikes occur multiple times during night, greatly reduced with age). This moleule can handle all ROS (oxygen based FR's) and NOS (nitrogen based FR's) except Superoxide (•O2-) and it's decay products from taking a free radical "hit" are themselves powerful antioxidants so that it can take an average of about 4 hits in succession. This is like a body guard who jumps in front of a bullet meant for you and then gets up again another 3 times to do the same. Even more powerful this antioxidant seems to have no upper limit in terms of damage to us. Some molecules like MSM (methyl sulfonyl methane) and melatonin have never been found to have any measurable toxicity.This is instrumentally involved in the ability of the dark (night) period to reconstitute our health for the following day. With age one should supplement with this molecule as it is profoundly protective !  Note that fertile females should avoid taking this as it is a regulator of most animal breeding times (set by the hours of sunlight that vary between summer & winter) . Another reason that fertile women should be cautious is the occurrence of female cancers when fertile female rodents are dosed with a sizable amount.

EXOGENOUS

Vitamin C - Most mammals can make this and drastically increase levels when infected or sick. Humans and guinea pigs have lost the ability to make Vitamin C and must get it from plant sources. The half life in blood is only about 30 minutes, so you should use a time release (buffered with citrus bioflavonoids) form that will not just rapidly be lost to urine. What you want is to constantly keep levels slightly elevated to best benefit your health. 

An adult goat, a typical example of a vitamin-C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and as much as 100,000 mg daily when faced with life-threatening disease, trauma, or stress. Stone, Irwin (July 16, 1978). "Eight Decades of Scurvy. The Case History of a Misleading Dietary Hypothesis". 

Vitamin E  - Fat soluble reducing agents that can terminate free radical chains in membranes (which can undergo massive increases due to repeated cyclic oxidation processes).Vitamin E is composed of tocoperols and the tropical variants called tocotrienols. These Trocotrienols (tropical vitamin E variants with multiple double bonded structures), just like tocopherols are slowly distributed to a variety of tissues from dietary sources. This process requires considerable time to build up a substantial level in a variety of tissues - about a year of taking at least 400 international units of supplemental vitamin E and tocotrienols.  

The vitamin E group of compounds is among the better known of the vitamins due to their suggested health benefits including antioxidant and related protective properties. Among these, tocotrienols have gained prominence in recent years due to their potential applications and better protective effects in certain systems. These tocotrienols are vitamin E derivatives that are analogs of the more established forms of vitamin E namely tocopherols. In addition to their potent antioxidant activity, tocotrienols have other important functions, especially in maintaining a healthy cardiovascular system and a possible role in protection against cancer and other ailments.  Multitargeted therapy of cancer by tocotrienols. Nesaretnam K.  Cancer Lett. 2008 Oct 8;269(2):388-95. Epub 2008 May 27.   http://www.ncbi.nlm.nih.gov/pubmed/18504069

Carotenoids - Produced by algae and plants, these pink to red to yellow pigments are a group that includes Vitamin A (a variety of carotenes are two Vitamin A molecules chemically bonded together). When the body wants more Vitamin A it can split various carotene to gain them. Note that we also have a need for direct intake of Vitamin A already formed, something we usually get form various meat sources (a problem for strict vegetarians - see SUBSCRIBER only "WHAT VEGETARIANS NEED TO KNOW" PDF.). Another non-Vitamin A producing version of an oxygen containing carotenoid is the molecule astaxanthin which has proved protective against inflammation and cardiovascular diseases well as brain injuries.

Oxidative stress and inflammation are implicated in several different manifestations of cardiovascular disease (CVD). They are generated, in part, from the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that activate transcriptional messengers, such as nuclear factor-kappaB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Despite this connection between oxidative stress and CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Pashkow FJ, Watumull DG, Campbell CL. Am J Cardiol. 2008 May 22;101(10A):58D-68D. http://www.ncbi.nlm.nih.gov/pubmed/18474276 < astaxanthin also gets past the blood brain barrier to provide protection in the brain >

 

http://www.nal.usda.gov/fnic/foodcomp/Data/car98/car_tble.pdf

FOOD
Lutein & Zeaxithin Lycopene a-carotene b-carotene b-cryptoxanthine
Broccoli (raw) 2445 0 1 779 0
Broccoli (cooked) 2226 0 0 1042 0
Brussel Sprouts cooked drained 1290 0 0 465 o
Carrots raw 385 (baby carrots only) 0 4649 8836 0
Collard Greens raw na, likely about same as cooked 0 238 3323 80
Collard Greens cooked 8091 na probably 0 30 4418 20
Cheese, cheddar 0 0 0 85 0
Corn Sweet Yellow Cooked fresh corn on cobb

1800 Avoid, likely comtaminatedwith GM genes

0 30 33 0
Eggs, raw fresh whole 55 0 0 0 0
Grapefruit pink & red 13 1462 5 603 12
Kale Raw 39550 0 0 9226 0
Lettuce (Romaine) 2635 0 0 1272 0
Lettuce iceberg 352 0 0 192 0
Mangos canned, drained na na na 13120 1550
Oranges 187 0 16 51 122
Peas green canned(drained) 1350 0 0 320 0
Peppers Red raw sweet raw na 0 59 2377 2205
Persimmons, Japanese raw 834 158 18 347 1447
Pumpkin, cooked canned w/o salt

0

0 4795 6940 0
Spinach Raw 11938 0 0 5579 0
Spinach Boiled w/o salt 7043 0 0 5242 0
Summer Squach (Zucchini) raw 2125 0 0 410 0
Tangerines, raw 243 0 14 71 485
Tomato red ripe raw 130 3025 112 393 0
Tomato red ripe Paste with salt 170 29330 29 1242 0
Tomato red ripe puree with salt 90 16670 0 410 0
Tomato red ripe canned whole 40 9708 0 186 0
Tomato Catsup 60 17008 0 730 0
Tomato juice w/o salt (unsweetened) 60 9381 0 428 0
Turnip Greens boiled, no salt 8440 0 0 4575 0
Vegetable juice Coctail 90 9660 210 830 0

 

NOTICE THAT YOU CAN GET MOST OF NEEDS FOR THESE VARIOUS CAROTENOIDS can be met with Tomatoes(lycopene), Spinach & (lutein&b-dcarotene),Kale (high in both lutein and zeaxithin, b-carotene) , Carrots or Pumpkin (a&b-carotene), and Red SweetPeppers or Mangos for b-cryptoxanthine.

Meats & poultry & cheese(except the very nutritious "eggs" that have some Lutein & Zeaxithin but no other major carotenes) have very little carotenoids (some b-carotene)
Salt Water Fish have some but not generous carotenoids (Salmon and shrimp are pink due to astaxanthin a very useful carotenoid that crosses the Blood Brain Barrier and to protect neurons in each. (additional to required the high stored level of lutein and zeaxithin in the macula or fine focus center of the eyeball)
Beans have very little carotenoids

Notice that some vegetables or fruits have only some of the needed carotenes and not others - we must eat several to cover our needs.

The common joke in American Medical Schools is that if you are a male and live long enough, then you will have prostate cancer. As is "SO COMMON" in this limited medical "knowledge", this is just not universally true in the world in general. It is believed by people knowledgable in the incidence of prostate cancer world wide, to be a function of the particular environmental conditions and in particular due to the types of food intakes that are protective OR NOT. Please note that additional to the comments in this quotation, zinc levels are also important as the prostate is the body' largest supply of stored zinc that is improtant in control mechanisms (zinc fingers in gene transcription http://en.wikipedia.org/wiki/Zinc_finger) and maintaining a healthy immune system. A you will learn in the SUPPLEMENT section. Zinc must be at the right level - both too little and too much are harmful (something commonly true to almost all the "second string" minerals).

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene <see red color in above table>, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. Can the Mediterranean diet prevent prostate cancer? Itsiopoulos C, Hodge A, Kaimakamis M. Mol Nutr Food Res. 2009 Feb;53(2):227-39. http://www.ncbi.nlm.nih.gov/pubmed/19051189 < in addition to lycopene & selenium, Vitamins E and D have also been found preventive against prostate cancer, these are facts you will never hear from your physician >

What can we learn as a take home lesson from this? Again, the best protection in a rainbow diet that also has a bias to some foods like dark leavy green vegetablesfor lutein and xeaxanthin (Kale, collard greens, spinach), tomato as a profound source of lycopene, carrots or pumpkin as an escellent source of a-& b-carotenes, and sweet red peppers as a source of b-cryptoxanthin. Additional to this we can take a supplement of astaxanthin as a profound protection for our cardiovascular and brain systems.

Flavonoids & Phenolic - This is a very large and very broad set of types of Hydroxyl-group ( R-OH ) containing molecules that are produced by plants & algae. In Plants and algae they quench all sorts of untoward free radicals, much like they do in us. Most of these are short lived when absorbed into blood (a half life of about 30 minutes in human blood is typical (There are exceptions that have much higher half life life times in the blood stream with “massive benefits” - see the SUBSCRIBERS ONLY PFD on ANTIOXIDANTS - SPECIAL).  in general flavonoids are quite stable in acid conditions, e.g. wine or vinegar solutions). One commonly used and extremely beneficial flavonoid antioxidant is ordinary Cocoa as in the bitter unsweetened chocolate power from the Cocao plant. This is sold in markets as as a baking ingredient to give that wonderful chocolate flavor and taste. Cocoa contains a series of covalently (chemically bonded) short chains (multiple molecules covalently bonded together) of the flavonoid quercitin that that the body can only slowly be lysed to free each quercitin flavonoid over a period of 2 - 4 hours. This makes our chocolate treat a time released antioxidant treat for both our taste buds and also for antioxidant protection of our tissues (use cocoa with stevia for hot chocolate or eat only high cocoa content (>60%) dark chocolate as milk chocolate has lower cocoa and much to much sugar). Understand that stevia sweetened hot chocolate or dark high cocoa value (60-80% cocoa) dark bitter sweet (lower sugar) chocolates are very good for you - they are literally health foods. Don't over do these as too much very high levels of flavonoids can be a depressant to your endogenous antioxidant protections. Beware of the level of fat and simple sugars you are getting. Milk chocolate and other rich sources of simple sugar sweetened chocolate treats are to be avoided - too high in sugar which will mess with your blood sugar and insulin status ! You will get the familiar sugar high followed by a crashing unpleasant sugar low.

Proanthocyanins - Dark color (black,blue,red) from various berries that are covalently linked flavonoid molecules that are too large to be absorbed mostly (some apparently are) into the blood stream and thus travel the gut tube where bacteria in the colon break them down to antioxidant flavonoids that constitute one of the few antioxidant protections in the colon. Another protection in the colon is the phytates (IP6) that bind metal ions that we covered when describing “Ty's ALL DAY ENERGYTM” from partially cooked grains in the DIET section. Note that both Proanthocyanins and their flavonoid monomers are able to act as metal binders to interfere with metal catalyzed cyclic oxidation patterns.

These following compounds deserve Honorable Mention for reasons that will be clear to SUBSCRIBERS in the CANCER - ALTERNATIVES PDF

Eugenol - As you will later see in the rating of natural existing antioxidants, eugenol which is some 85-95% of Clove oil is by far the most potent antioxidant in nature. This compound like most of the phenolic antioxidants has a half life in blood of only about 30 minute, but can be sipped in a tea (very dilute - 4 drops per pint(half liter) not more and violently shaken to mix thoroughly). This molecule also has remarkable cancer killing abilities that are covered for SUBSCRIBERS in the CANCER - ALTERNATIVES PDF

-D-Limonene - a-D-Limonene (named for lemon) is most abundant in Orange Oil where it constitutes some 90-95% .a-D-Limonene is not a extremely powerful antioxidant, but it has properties that make it worthy of attention. This compound has been used in human clinical trials against cancer (successfully) and has the the wonderful property of acting much like Vitamin A in differentiating cells into terminal (undividing) status. It literally differentiates to final undividing status cancer cells (including cancer stem cells). This is covered for SUBSCRIBERS in the CANCER - ALTERNATIVES PDF.

There at two different activities ongoing in these radical prevention reactions. The first is a radical quenching which we have been focused on with classic Flavonoid, eugenol, Vitamin C (ascorbic acid), Vitamin E (tocopherols & tocotrienols), The second is binding of potentially reactive metals to prevent cyclic processes of continuous chain reaction radical formation (melatonin, glutathione, a-Lipoic Acid and Flavonoids) (analogous to the lipid peroxidation in membranes despite a different catalyst (metal ions). In this second case, many of the excellent quenching antioxidants (that do not bind and prevent metal cyclic reactions) may contribute to the cyclic processes of oxidative damage. This is very important because some (many) anticancer agents use cyclic free radical generation to produce high (lethal) radical load in cancer cells. Many types of free metal ions generate similar cyclic radical production ( iron Fe, copper Cu, chromium Cr,  lead Pb, mercury Hg, nickel Ni, and vanadium V as starters) . Some antioxidant quenchers are also metal binding (melatonin, glutathione, a-Lipoic Acid, & Flavonoids). We need both protections to avoid both types of free radical generation in our cells. 

More recently, coordination of sulfur and selenium compounds with metal ions has been proposed as an additional antioxidant mechanism [12, 13, 15, 16]. Collins et al. have reported selenium­copper complexes that utilize both metal binding and ROS scavenging in oxidative stress prevention [28]. Our research has demonstrated that metal coordination is required for inhibition of copper- and iron-mediated DNA damage by sulfur, oxo-sulfur, and selenium compounds [12, 13, 15, 16]. Metal binding as a novel antioxidant mechanism for sulfur and selenium may be complementary to ROS scavenging and GPx activity. Antioxidant activity of sulfur and selenium: a review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms. Battin EE, Brumaghim JL.  Cell Biochem Biophys. 2009;55(1):1-23. Epub 2009 Jun 23.   http://www.ncbi.nlm.nih.gov/pubmed/19548119

Now we know we need both antioxidants that can directly act against radicals (So called "Type I" antioxidants: glutathione melatonin,Vitamin C, E, carotenoids, Eugenol, etc.) and protective antioxidants that can also bind free metal ions (So called "Type II" antioxidants: melatonin, glutathione, a-Lipoic Acid ) so that we can prevent the unwanted cyclic generation of free radicals.  Further, we can boost our glutathione levels by taking the very inexpensive compound called MSM ( Methylsulfonylmethane (CH3)SO2) that is routinely used by people for joint problems. This has been found to boost the glutathione levels in rat liver by some ~80% (http://www.fasebj.org/cgi/content/meeting_abstract/22/1_MeetingAbstracts/445.8). The liver in mammals is the major synthetic organ. This effect was not seen in lungs or muscle tissue. (Alternatively we can use whey protein powder that is rich in sulfur amino acids or we can use a lot of garlic which is also high in sulfur compounds). Since we can supplement with most of these and avoid having to purchase the VERY EXPENSIVE glutathione or a-Lipoic Acid we will gain benefit without going broke! The reason we don’t use supplemental a-Lipoic Acid lies in it’s expense and that most cellular a-Lipoic Acid is bound to the proteins it serves. This is much less true for diabetics who greatly benefit from taking supplemental a-Lipoic Acid ( http://www.ncbi.nlm.nih.gov/pubmed/19019027  ). Carnosine is an excellent sacrificial preventer of glucose from covalently binding to vital proteins like hemoglobin (called glycation and reported as A1c numbers which represent the % of a hemoglobin molecule that has suffered glycation), but if we use Ty's ALL DAY ENERGYTM with " time release whole grains", we will never have high levels of glucose in our blood to promote this bad reaction. Keeping your blood sugar low (and insulin levels low as a consequence) is fundamental to a Longer Healthy Life and to avoiding needless problems.

We also want to have higher levels of antioxidant protection than is typical with an ordinary good diet. This has been found to increase the healthy period of life without increasing our longevity. Clearly, free radicals which oxidize a higher fraction of our proteins with age, leave us less able to handle the ordinary stress of life. These damaged proteins and “gone bad mitochondria” accumulate because we do not often enough encourage fasting periods where TOR gene is at a low enough level to encourage AUTOGAPHY. This is a problem we can solve with periodic fasts and with the use of centrophenoxine (contains a covalently bound DMAE) or DMAE (dimethylaminoethanol) that helps our cells dispose of this toxic garbage. The DMAE compounds help to get rid of the garbage that collects in our cells - which is often called lipofuscin (http://en.wikipedia.org/wiki/Dimethylethanolamine http://www.lef.org/anti-aging/chap7.htm http://www.antiaging-systems.com/extract/centrophenoxine.htm   http://www.antiaging-systems.com/a2z/centrophenoxine.htm). We will cover DMAE and centrophenoxine in the SUPPLEMENTS section.

In the last century, dense, pigmented bodies were observed on nerve cell sections, and the quantity of those pigments in the neurons was correlated to the age of the individual. Light microscopy has shown the presence of the pigments in the cells of most tissues and organs in both vertebrates and invertebrates, and they have also been seen in cultured cells. However, these commonly found cellular components have only have studied in detail since the last 25 years, using electron microscopic, histochemical and biochemical techniques to try to describe their nature, origin, development and possible physiological role. The comparable morphology, composition and physicochemical properties of these various pigments indicate that they are all produced by the same biochemical mechanism, including: 1) the peroxidation of the polyunsaturated fatty acids of cellular membranes by free radicals; 2) the reaction of lipid peroxidation end-products(s) with proteins, giving fluorescent polymerized compounds; 3) the combination of those polymerized elements and the peroxidized lipids. Different names have been used for these pigments, the most common of which in English are: "age pigment", "ceroid" and "lipofuscins". However, due to their common origin and their fluorescence, they are tended to be grouped under the term lipofuscins (in French: lipofuscines). Recent studies have confirmed that cellular lipofuscin concentration is definitely related to the physiological age of the individual. This concentration varies depending on the tissue and the organ; it is controlled by intrinsic regulatory factors, but also by environmental conditions, such as nutrition, physical activity, stress and hygienic conditions.   Polyunsaturated fatty acids and aging. Lipofuscins : structure, origin and development. Durand G, Desnoyers F.   Ann Nutr Aliment. 1980;34(2):317-32.    http://www.ncbi.nlm.nih.gov/pubmed/7001991

You now pretty much have the keys to the kingdom of FREE RADICAL PROTECTION. We will detail the specific amounts and best sources in the SUPPLEMENTS section.  The way to a Longer Healthy Life is through knowledge that drives action. Don’t just know it - DO IT !

Higher levels of balanced antioxidants generally lead to higher insulin sensitivity as well (http://www.ncbi.nlm.nih.gov/pubmed/8480681), however, there is a little problem. That problem is that the body has a set point for free radical load. That is to say, if the combination of ENDOGENOUS and EXOGENOUS antioxidants is greater than this set point, these control mechanisms will down regulate the ENDOGENOUS antioxidants. This is in part a regulatory set point to inform the body of the level of free radical oxidation problems because we still need free radicals as a informing signal to control various metabolic and synthetic processes. The body uses changes relative to this set point to increase or decrease ENDOGENOUS antioxidant levels and then radical activity then returns to this set point. Since the mitochondria is the energy powerhouse of the cell, most free radicals are created there. This balance is one of the reasons why we cannot increase our life spans by just increasing the level of EXOGENOUS antioxidants.

When we do exercise, we improve our radical handling capabilities for about a full day or two with a decline to almost no benefit after two days. You cannot save up this benefit. This improved antioxidant benefit is paralleled by a substantial improvement in INSULIN SENSITIVITY (http://www.ncbi.nlm.nih.gov/pubmed/19927140 http://www.ncbi.nlm.nih.gov/pubmed/19056588 http://www.ncbi.nlm.nih.gov/pubmed/18171435). When you remember back to our central theme that maintaining excellent Insulin sensitivity (low insulin levels and thus low TOR levels) is the CENTRAL CONTROL OF THE LENGTH OF OUR LIFE SPANS, you can see how EXERCISE is so  important  for our good health and longevity. So, what we have to do is find a clever way to gain the best of both high ENDOGENOUS and high EXOGENOUS (supplemental as well as dietary antioxidants). However, when we are using “above” dietary levels of these supplemental antioxidants we will have down regulated some of our ENDOGENOUS antioxidants.

Exercise in good for you. Exercise can massively increase insulin sensitivity by up to 30%. The problem is that when young men take  high levels of vitamin C (500 mg/day) and vitamin E (400 IU/day) and exercise - they do not get the same insulin decline and better free radical handling which does occur without these supplemental vitamins, the antioxidant vitamins blunt the rise in insulin sensitivity from exercise.

"exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans "  Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70      http://www.ncbi.nlm.nih.gov/pubmed/19433800

"Surprisingly, use of antioxidant supplements blunts the beneficial effects of regular exercise on insulin sensitivity, even though diets that are rich in fruits and vegetables (and, thus, contain high concentrations of antioxidants) lower risk for developing type 2 diabetes " Antioxidant Supplements Blunt Exercise-Induced Improvement of Insulin Sensitivity  Journal Watch General Medicine June 4, 2009  http://general-medicine.jwatch.org/cgi/content/full/2009/604/1

The reason for this apparent anomaly lies in the nature of our antioxidant defenses. We have both ENDOGENOUS and EXOGENOUS(Vit E,C,carotenes,flavonoids) that protect us from too high a level of free radicals. The best way to visualize the relationship between these two antioxidant protections is as a additive level needed to maintain a low and tolerable level of Free Radicals. Yes, we need free Radicals to signal cell events and controls( http://www.ncbi.nlm.nih.gov/pubmed/19486941 http://www.ncbi.nlm.nih.gov/pubmed/19187004 ). The body has a range of values of free Radicals that it tolerates, but no more, after that it turns on ENDOGENOUS antioxidant production to return to the set point. Biology uses many different mechanisms to trigger signals, and free radicals are one of them. By feedback mechanisms, when there is an elevation of free radical levels above the necessary set point levels, the body will induce higher enzymatic activity and higher synthesis of the ENDOGENOUS group of protections. Note that, in the absence of illness, we always have a small reserve in antioxidant protection above the level of dangerous radical levels.

When you exercise without any high levels of EXOGENOUS (Vit C,E,caortenes, flavonoids) antioxidant protection, exercise ITSELF elevates free radical levels above this tolerated level.  The long term genetic WISDOM OF THE BODY will cause an elevation of both enzymatic activity and of the synthesis of these ENDOGENOUS anti-oxidant protections. From this comes the improved health effects of better insulin sensitivity which is a combined effect of lower free racial levels and better functioning membrane transduction systems (cellular membrane fluidity dependent ability to send and act on cascades of biological signals - like mobilize glucose transporters involved in clearing the blood of excess glucose.)

When you take higher levels of balanced EXOGENOUS antioxidants via supplements and diet choices, you have given yourself a bigger buffer against rise in free radical levels. This buffer makes your body reduce the level of ENDOGENOUS antioxidant production and activity but the buffer of extra protection is higher due to the EXOGENOUS antioxidants. So the critical limits of elevation of free radical levels are not reached in moderate exercise - and you do not induce higher activity and synthesis of ENDOGENOUS antioxidants nor improved insulin sensitivity. 

So, are we we trapped to stay at this level of free radicals no matter what we do to do? 

NO !  As you will learn in the section on EXERCISE & Z's, we can do a very short term high level of effort exercise that causes our body to experience a temporary over production of free radicals - even though we have this high buffer level of EXOGENOUS antioxidants. This is exactly what is occurring in normal moderate exercise without additional (supplemental) antioxidants but at a lower level of exercise intensity. What this technique requires is a short period of very high energy out put. This "interval training" is normal for anyone attempting to improve physical strength.  For example, I put on my 30 lb. backpack of computers & books and run up 8 flights of stairs as fast as I can. I'm a real sweating panting and exhausted mess at the top of the stairs. But I have triggered the WISDOM OF THE BODY to increase activity and make more ENDOGENOUS antioxidants with a very short 3-6 minute very high exertion - despite the fact that I take a lot of EXOGENOUS antioxidants. Note again -this is despite the fact that I take high level of supplemental antioxidants and eat antioxidant rich food. Note that we are not going to be injured by a short term increase in free radical levels. What we get instead is nearly a whole day's period of much higher ENDOGENOUS antioxidant activity and much lower free radical damage as well as improved INSULIN SENSITIVITY.  And we get it on top of the higher level of EXOGENOUS antioxidant protection. Repeat each day for profound benefits - the same trick works every time. If you understand Mother Nature, you can trick her for your benefit. 

Since most people are not in physical condition to do this, you will have to follow the gradual increase in healthy physical conditioning suggested in the EXERCISE and Z's section. Please, no over-estimate your physical abilities, that leads to injury or serious medical complications. Return to a strong, healthy & lean fit status requires time and practice. Don't be a weekend "warrior" who injures yourself. The goal of our lives is a process of growing stronger and wiser, not blowing out. The PACE exercises suggested by Dr. Al Sears in the EXERCISE and Z's section explains the gradual process of progressive increase in your physical ability by this slow process of increasing short term exercise intensity with time. Dr. Sears advertisements tells of a woman who could not stand more then under a minute of ordinary walking, but gradually became stronger and stronger until she can easily run and exercise today. Doing this resulted in a massive loss of weight and and equally massive increase in health. For this you don't need a gym membership or some fancy exercise machine - just a determination and a willingness to do a gradual increase in your strength and health.

BEFORE YOU DO ANY INCREASED EXERCISE, YOU SHOULD CONSULT WITH YOUR PHYSICIAN ABOUT THIS. WHILE THERE TAKE A GOOD LOOK A HIM OR HER AND ASK YOURSELF - DOES THIS PERSON KEEP FIT AND PREVENT THE INCREASE IN FAT WITH AGE THAT IS A HALLMARK OF DEVELOPED SOCIETIES?

Below is a Graphic illustrating How we are OVERCOMING THE BODY’s SET POINT For about a day or two. 

 

Activation of nuclear factor (NF) kappaB and mitogen-activated protein kinase (MAPK) pathways < control cascades in our cell > in skeletal muscle has been shown to enhance the gene expression of several enzymes that play an important role in maintaining oxidant-antioxidant homeostasis, such as mitochondrial superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS). While an acute bout of exercise activates NF kappaB and MAPK signaling and upregulates MnSOD and iNOS, administration of chemical agents < supplemental antioxidants > that suppress reactive oxygen species (ROS) production can cause attenuation of exercise-induced MnSOD and iNOS expression. Thus, ROS generation during exercise may have duel effects: the infliction of oxidative stress and damage, and the stimulation of adaptive responses favoring long-term protection. This scenario explains why animals and humans involved in exercise training have demonstrated increased resistance to oxidative damage under a wide range of physiological and pathological stresses.  Role of nuclear factor kappaB and mitogen-activated protein kinase signaling in exercise-induced antioxidant enzyme adaptation. Ji LL, Gomez-Cabrera MC, Vina J.   Appl Physiol Nutr Metab. 2007 Oct;32(5):930-5.  http://www.ncbi.nlm.nih.gov/pubmed/18059618

Why does this work for us?

We are not certain but a critical fact is that we have two types of Superoxide dismutase molecules(SOD’s) that destroy superoxide ( •O2-). There is a short half life Copper/Zinc based cytoplasmic type of SOD (6-10 min for Cu SOD http://www.ncbi.nlm.nih.gov/pubmed/0484504) and a much longer half life (some 5-6 hours http://www.ncbi.nlm.nih.gov/pubmed/0484504) mitochondrial located Manganese based superoxide  dismutase. Thus in 12 hours the mitochondrial MnSOD has declined to a quarter of its high  value and so on until it is diminished to the set point. It is not actively destroyed but must decay by half life. This is not proven, but remains likely as the primary cause of exercise induced improvements in ROS/free radical handling and hence the temporary improvement in Insulin sensitivity of a day or two)

What we are doing is to create a sufficient stress via exercise to temporarily raise radical levels to over come our high level of ENDOGENOUS + EXOGENOUS protection. The body reacts to as a dangerous radical overload that must be dealt with by greatly boosting the ENDOGENOUS antioxidants. So after this exercise, we have a restored higher level of ENDOGENOUS antioxidants (they were way down before exercise because of the high level of EXOGENOUS antioxidants) but rapidly the ENDOGENOUS were synthesized to a much higher level of ENDOGENOUS antioxidants. THIS  IS THE BEST OF BOTH WORLDS ! Remember we have recharged the exhausted EXOGENOUS antioxidants as well).  But improvement in levels of the ENDOGENOUS mitochondrial Mn SOD by our exercise burst lasts only till the decline back to normal set point levels. What is the solution to this?

Exercise (PACE technique of short progressive increased effort) at least every other day !

YOU CAN OVER COME THE BIOLOGICAL SET POINTS OF RADICAL LOAD FOR YOUR BEST HEALTH - ENJOY A HIGHER INSULIN SENSITIVITY, A STRONGER MORE RESILIENT BODY AND PROBABLY DO A BETTER JOB OF IMPRESSING OTHERS WITH YOUR PHYSICAL HEALTH.   ----- WOW !

 

NOW THAT WE UNDERSTAND HOW TO PROTECT OURSELF WITH ANTIOXIDANTS AND EXERCISE, LETS GET BACK TO DIETARY COMPONENTS THAT OFFER LARGE PROTECTION............ FOR THIS WE WILL USE THE FDA DEVELOPED “ORAC” SCALE. 


 ORAC Scale 

ORAC stands for Oxygen Radical AbsorbenceCapacity (ORAC) and designed to be a measure of the ability of a fixed amount of food or other nutrients (100g) to prevent a standard amount of added radical generating material from creating free radicals that will show up as lysed fluorescent color (which can only be fluorescent when the chemical bond is broken. The test involves generating in a test tube  a fixed amount of  peroxiradical that has to be quenched to avoid freeing the test fluorescent color. 

This leads to data about the ability of each different type of food or compound to resist  or quench the peroxiradical and prevent or diminish the occurrence of the fluorescent colored compound that can be easily monitored spectrophotometrically. The whole 100 grams (about 3.5 ounces) is not used, just enough to calculate what it would  represent. When you do this for many different dietary sources and spices, oils, etc. you get the chart below. This is a semi-logarithm plot so each unit is a factor of 10 up. This means we are massively compressing much larger variation for the purpose of fitting it all on one chart. When we use the standard cartesian linear axes, we get the chart seen in the upper right corner which show only the huge magnitude of Clove oil (Eugenol) and every thing else is at the bottom. After this graphic presentation (again with compressed semi-logarithm structure), you can see the actual numeric ORAC values by clicking on the SEE ORAC NUMBERS LIST.


SEE ORAC NUMBERS LIST

MORE DETAILS ON THE ORAC TEST (SKIP over THIS TO the next INFO ON FRUITS & VEGGIE BENEFITS (next heading)- UNLESS YOU ARE REALLY INTERESTED)

ORAC testing is performed in a test tube that compares a precise dilution of a sample with a parallel series of samples of a standardized "Vitamin E like" but water soluble compound called Trolox. The indicator is a flourescein dye (gives off a different color light when irradiated by another wavelength (color)of light) that is hydrolyzed to colorless by free radicals. These test tubes are then spiked with a fixed amount of a peroxyl radical and allowed to incubate for 35 minutes with measurements of this indicator dye at regular intervals. A plot of the decline in the dye fluroescence with time is produced and the integrated area under the graph is compared to the standards. This is a kinetic comparison over some 35 minutes, so foods with fast acting and slow acting antioxidant activity will be captured by this measurement.

ORAC values do not take into account  processing of various antioxidants to altered but still active (or more active) forms in the cells of the body, nor do they simulate the different bioavailability due to poorer absorption in out gut. ORAC also only measures the original antioxidant capabilities within a test tube and against a particular type of free radical called a peroxyl radical. Originally, ORAC was only designed to detect aqueous soluble antioxidant activity, but we now have variations that test lipid (fat) soluble and aqueous soluble separately and also report the total value. The data below are in ORAC units per 100 grams of food.  

More refined testing methods now in process will differentiate between the main classes of biological free Radicals: hydroxyl radicals (OH•, measured by HORAC test) ,  superoxide radical (•O2-), hydrogen peroxide, singlet oxygen (1O2, from UV-A sunlight exposure), and peryoxynitrile radicals (NO2• oxidized from NO• original, NORAC test) from the biological modulator NO (nitric oxide). Different antioxidants have different  capacities to trap these different types of free radicals.

Some antioxidants are ampiphilic molecules, soluble in  both fat and water. Thus they can provide both lipid and aqueous protection, but many other classes do not have significant either lipid or aqueous protection. The separate functions can be visualized as effective in the aqueous or olive oil regions of a vinegar/olive oil two layer system.  An example of this is the carotenoid class of compounds (b-carotene, lutein, zeaxanthin, astaxanthin, lycopene, etc. that give fruits the yellow and pink-red colors). Fat soluble carotenoids have very low levels of water soluble ORAC results and very high levels of fat soluble ORAC results. Experts like Lester Packer at UC Berkeley use carotenoid levels in tissues to determine the overall antioxidant protection in different human individuals. 

In general, the dark blue, purple and black colored fruits have anthocyanins which are covalently joined molecules of flavonoids that are not very bioavailable,  while vegetables and grains usually have a differing mix of flavonoids and anthocyanins. Anthocyanins are the only antioxidants left in food after it has transited the small intestine, and are broken down to effective flavonoid type antioxidants in the colon conferring needed antioxidant protection there (colon cancer is rising in western countries REF T).

ORAC values for any given fruit or vegetable can vary with harvest timing, weather variations, temperature, ripeness, and soil conditions. It is wise to take ORAC values with a 10-20% variability depending on the particulars of the plant source. Another important aspect of biological benefit is the ability of human uptake (bioavailability). Further, the standard way of reporting ORAC values is per 100 grams (@ 3.5 ounces) of material. Many commercial producers of antioxidant mixtures report ORAC values for other serving sizes, etc. The FDA has slowly upped ORAC suggested intake per day from 3000 to 5000 ORAC units. We do not know if or when we are at maximum value for maximum biological benefit. CHECK HOW FAR OUT MEASURED BLOOD LEVELS from BOLUS? These suggested values are what is now believed to be where we no longer see benefit, however this may not be real optimums.  We will probably have to do a kinetic blood based analysis to gain a better value due to varying bioavailability, but this is a much more extensive testing sequence which has it's own problems of individual uniqueness and inclusion of down stream metabolized products that can have more or less antioxidant activity.


This absence of broadness to measure a wider range of various antioxidant contributions has led to some dissatisfaction with the ORAC test alone as it is non-inclusive of the wider range of antioxidant protections. It is also possible to hype ORAC levels in commercial product by adding large amounts of green tea or grape seed extract and other high ORAC value but lower cost components. That said, ORAC values of amphiphilic (Total or fat and aqueous soluble antioxidants) is rather a good indication. These are usually small molecules like the eugenol that is some 85-95% of 'oil of cloves'. We will have much more to say about eugenol (oil of cloves) to SUBSCRIBERS .

In all cases, a broad intake of different antioxidant types via a broad intake of different whole food sources is the best protection. A huge amount of nutrition benefits is ignored by just looking only at ORAC values, but do indulge high ORAC foods as well.  While you can get much higher ORAC values by consuming extracted oils or spices or "supplements", whole foods seem to be the best choice and even better when supplemented by these oils and spices. Many beneficial health properties of antioxidants are not always obvious from ORAC values alone. Each vegetable or fruit contributes an amazing array of beneficial molecules which are also needed for good nutrition. One can also take supplemental levels for some or many antioxidants, but the bottom line is a healthy diverse diet of minimally cooked or not cooked foods is ideal. You should cook meats, poultry, fish, eggs, and unsprouted dried beans, etc. as protection against food related pathogens and antinutritients in beans. 

How Fruit Colors relate to IMPORTANT ANTIOXIDANT COMPONENTS

Fruits colored dark Blue, Black, Intense Indigo/Violet are usually rich in proanthocyanins and flavonoids. (E.g. Blackberries, blueberries, prunes, plums, raisins, dark seeded grapes, even black and red raspberries)

Fruits that vary form pink to yellow to orange often are very good sources of carotenoids (From mangos, papayas, citrus fruit (esp. lemons and grapefruit, oranges), cantaloupe, pumpkins, carrots, tangerines, apricots

Dark leafy green vegetables are very rich in chlorophyll, minerals, B-vitamins, lutein (& zeaxanthin in case of kale), and often indoles and other anti bacterial and anti-cancer compounds as well as rich in antioxidants. 

Spices

Spices are very high in protective antioxidants and other benefits. All the Italian herbs are excellent (particularly rosemary and basil that tend alone with celery seeds to reduce inflammation and basil and thyme to protect the skin, oregano is possibly the highest antibacterial spice in existence, certainly rivaling garlic). Cumin and sage are noted for their excellent maintenance of brain health. Cayenne, cinnamon (no more than 1/4 teaspoon per day of cinnamon** as has very potent but somewhat dangerous cinnamonaldehyde), and coriander are good for blood sugar and minimizing obesity. Turmeric, ~50% of which is the flavonoid curcumin that is used as an anticancer compound, but it is far better to use as a preventive spice. 

** the blood sugar lowering effects of cinnamon come from the aqueous soluble portion which can be prepared by steeping cinnamon in boiling hot water, then filtering out solid cinnamon and freezing the water in an ice cube tray. Covered in the SUPPLEMENTS section. Or you can buy the mixture called Cinnulin which is done the same way.

SUPPLEMENTAL IDEA  

Strong antioxidants may not just have benefit as antioxidants because high ORAC value antioxidants are extremely effective antimicorbials with different selectivity against various fungi, bacteria, and viruses. The causes of death in 1900 were mainly bacterial infections ( ~ 90%) with very dangerous pathogens (diphtheria, etc. - eliminated by mainly public health measures (clean food and water and public awareness of avoiding infections). Perhaps a new benefit of consuming high antioxidant (ORAC) value foods will be getting rid of CURRENT endemic biological parasites (like mycoplasmas) and other immune escaping bacteria/viruses. This may be some of the benefit conferred by the very high ORAC value supplements (e.g.. Clove oil and various spices, garlic).

Could the problems caused by these rogue microbial endemic infections be part of the cause of the acceleration of aging (along with nutritionally driven developing imbalance in dynamic insulin hormonal homeostasis maintenance?  We don’t know yet ! But eating a few high ORAC spices and Oils (Eugenol via Clove oil) just might be the ticket). If not - then at least you had a great taste treat.