Free Radical theory of disease

While this "new" theory is not necessarily my idea, it has many proponents and the allopathic world is slow to accept what the biochemists have known for years. Before we get into discussing the various disease states and their associations with free radicals, it would be prudent to give some basic chemistry background on free radicals.


What is a free Radical?

Simply put, it is any chemical species that has an unpaired electron in one of it's orbitals (generally the valence or outer shell). Nature abhors an unpaired electron, except for hydrogen, but this is true for any elemental atomic species, and indeed these parings drive many of the chemical reactions that help to fill the valence shell to the proper number when it concerns a compound. When these atoms come together to share electrons to provide a full valence shell, we cal this a covalent bond. There are, however, ionic bonds but these are more due to electronegativities of the atomic species involved and beyond the scope of this article. A free radical happens when a molecule with a covalent bond loses 1 electron from a complete orbital. This electron really doesn't go away it just gets released to another species, so now we have a molecule that has an "unpaired" electron. This is because orbitals can contain only two electrons with opposite spins, again beyond the scope of this article. So now we have this molecule that has an incomplete shell orbital that is dying to get its hands on an electron to help fill it's need. This free radical now goes and steals one from another molecule that is more willing to give one up and thus becomes satisfied, but now the victim molecule has become a free radical! This goes on for quite some time, robbing Peter to pay Paul so to speak. We, therefore, call this the chain reaction of free radicals. I'm not mentioning ions (single atoms) as free radicals, although in the strictest sense they are, but rather limiting my discussion to molecular compound free radicals, that is, compounds that keep thier bonds but lose electrons.


What causes free radicals?

We've already discussed one cause, that is another free radical. Another cause can be an energy source that is strong enough to release an electron from its stable configuration. These sources can be ultraviolet, microwaves or conventional heat (although it takes a lot of this to forcibly break a single electron from an orbital, most likely the bond will break first), basically anything in the electromagnetic spectrum at high frequencies will release an electron from its orbital. In a biological system we see that transition metal catalysts provide a mechanism for some radical reactions and these reactions can produce, among other radicals, hyroxide and hydrocarbon radicals. Also in biological systems there are many types of radicals, but the more "famous" ones are that of superoxides and intermediate chemiacl species. In chemical equations they are denoted with a dot next to them to suggest that there is an unpaired electron.


Reduction/Oxidation or redox

Reduction is the act of neutralizing a free radical (adding an electron) or adding a hydrogen atom to a compound to reduce double bonds between atoms. Oxidation is the act of removing an electron from a stable orbital or reducing the number of single bonds and increasing the number of double bonds, this is usually done by either removing a hydrogen or by adding an oxygen sometimes both, thus the name oxidation. Redox potential is the ease of being oxidized or reduced (simply put).


Antioxidants

What's the difference between a compound and an atom that has an extra electron (negative ion) and an antioxidant, strictly speaking, nothing, but we can't fill up the body with negative ions. Most antioxidants have what is known as conjugated double bonds. This is where carbon to carbon double bonds exists every other carbon so that single and double bonds alternate, see picture 1. As a matter of fact the more conjugated the atom the darker the color thus beta-carotenes are yellow to orange in color and red grapes are even darker. What makes the conjugated double bonds act as free radical neutralizers? Again I'll have to impart a little chemistry background. Double bonds are the connections of two atoms that occupy more than one orbital, in these orbitals are electrons. There are orbitals that are s and p types (among others), double bonds contain two p orbitals; these p orbitals exist in 3D space above and below the s orbital. When there is a conjugated system these p orbitals will line up and the electrons in them will tend to move about the shared orbitals, this is known as a PI electron cloud, for the electrons don't particularly belong to any one specific atom. Conjugated double bonds exist mainly in carbon chains as is evident in picture 1 where we see vitamin A. When a free radical comes along, the antioxidant will readily give up an electron, but still be stable due to the conjugated bonds, even though that now, this is a free radical itself, but hundreds of times more stable than a hydroxyl radical, let's say (OH· ).


In the antioxidant world there is a cascade of events that happens so that the antioxidant, that has become a free radical, can become a reduced antioxidant once again. Pools of Vit E will help Vit A and these will help other lipid (fat) soluble antioxidents and so forth, so what's important here is that a complete spectrum of antioxidants are taken multiple times per day to keep the antioxidant cascade in line and working. There's one special antioxidant that exists, that when it gives up an electron, it does not become a free radical, but rather a stable atom, and this is known as a hydride, that is, a hydrogen with an extra electron. This is possible due to the fact that the first orbital, the s orbital, can have a max of two electrons and since hydrogen only has one electron in its only orbital it can handle an extra one and yes it is an ion.


Consequences of free radicals


Why do free radicals cause damage? Ostensibly they change the molecular characteristic of the victimized molecule, so this in turn effects it's ability to bind properly which can affect all kinds of biochemical reactions, some having to do with the genetic expression of one protein or another. Oxidative damage, another name for the chemical reaction that free radicals cause, can lead to a breakdown or even hardening of lipids, which make up all cell walls. If the cell wall is hardened (lipid peroxidation) then it is impossible for the cell to properly get it's nutrients, get signals from other cells to perform an action (such as firing of a neuron) and many other cellualr activities can be affected.

One such interesting consequence of free radicals comes from our own immune system. Neutrophils secrete a chemical toxin that attacks a foreign invader (after a complex immune response has already started) and thus causes the foreign cell complex to lyse (break apart) and thus releases the invader toxins into the surrounding tissue. This not only signals the body to respond with more immune response to increase local inflammation to help neutralize these toxins, but these immune cells use antioxidants (chiefly Vit C) to protect themselves from their own toxins, fascinating stuff.

The cytochrome p450 pathway converts harmful hydrocarbons to alcohols that then can be eliminated by the liver. It does this because cytochrome p450 is what is known as a porphyrin ring that contains iron (Fe V) within its structure and this iron oxide extracts a hydrogen from the hydrocarbon and becomes FeOH and now the hydrocarbon is a radical. In the next step the OH radical dissociates from the Fe to combine with the hydrocarbon radical to create alcohol, which then goes through the alcohol dehydrogenase pathway to eventually get eliminated 1.


Some Antioxidants

Vit C – Also known as ascorbic acid. The most bioavailable form of Vit C is Ester-C, it has been shown to last longer in the body and comes with calcium (10% of the weight of Vit C) as this helps with cellular uptake. Humans, other primates and guinea pigs are the few animals that CANNOT synthesize Vit C as we lack a critical enzyme in the synthesis. 1-2 grams daily maintenance, 4-6 grams during active infection.

Good for : fighting stress; detoxifying poisons; antiviral properties and antihistamine (this is the inflammation response I talked about); repair and growth of tissue cells, blood vessels, teeth and bones; prevention of viral and bacterial infections.

Deficiency symptoms : Appetite loss; bruising easily; fatigue; GI problems; nose bleeds, slow wound healing; bleeding gums (loose teeth usually accompany this).

Vit E – alpha tocopherol, also important and should be consumed with the alpha form is the gamma form, gamma-tocopherol. So your best bet here is to consume a mixed tocopherol product of which there are several. Enhances the activity of Vit A (since both of these are lipid soluble). 400 IU maintenance daily, 800IU during detox or active infectious periods. Its important not to take too much as this vitamin will hang out longer due to the fact that it is lipid soluble and is excreted less easily.

Good for : endurance; protecting the lungs against pollution; anticoagulant (be careful if someone is already on an anticoagulant); accelerating the healing of burns.
Deficiency symptoms : Muscle degeneration; reproductive disorders; miscarriages; premature or low birth weight in infants, anemia.

Vit A – retinol – derived from the cleavage of beta-carotene, very similar to lycopene, discussed later. 10,000 IU for maintenance; 25,000 IU daily during active infection.
Good for: healthy function of intestinal flora, sinuses, ears, eyes, urinary tract, and respiratory organs; reduces duration of disease; healthy skin, hair; treatment of acne and boils (note the allopathic application of Retin-A, an analog of retinol); helpful in the treatment of emphysema.
Deficiency symptoms : ear, sinus, and eye infections; anemia; lower resistance to infections.

CoQ10 – coenzyme q 10 – a quinone found in the mitochondria of every cell. Carries electrons in the electron transport chain. This is extremely important for cellular energy. Heart cells require the most energy and thus CoQ10 is found in the most abundance here.
Good for : low energy levels, heart troubles (especially where there is muscular insufficiency). Applied topically actually reduces photoaging2 ; may actually modify cancer mediated cytokines (messengers). Helps in recovery of heart ischemia3

Deficiency symptoms : This is hard. How does something that is ubiquitous (thus the name ubiquinone) throughout the body manifest itself in deficiency symptoms as these symptoms could manifest themselves as almost anything. All that is really known is that as we age we tend to lose this cofactor for whatever reason. So as a general aging supplement it is recommended that one take between 30mg to 500 mg daily. 30-100 mg maintenance 200-300 for persons with heart disease, 400-500 for persons suffering cancer. Now the caveat here is that you are supposed to discuss this with your physician, but be aware that most physicians are unaware of the benefits of this "vitamin". Fortunately the thinking that taking antioxidants during cancer therapy will "offset" the therapy is falling out of favor with the allopaths, especially those that have had any nutrition course during med school.

Lycopene – This molecule is so similar to Vit A in structure that recent research has lost focus on the analog properties of this nutrient versus Vit A. Found in concentrated tomato products. How much to take, well that hasn't been established yet, but 10mg/day would be a minimum.
Alpha Lipoic Acid – AKA Lipoate - Vitamin like cofactor bound in mitochondria. Here's another cofactor found in and around the mitochondria. This lipoate has had excellent effects for neurodegenerative processes and diseases. It does this by raising the glutathione levels. Glutathione is an extremely important biological compound that destroys harmful oxidizing agents, it does this by reducing them (adding a hydrogen), but in the process forms a disulfide bridge to another oxidized glutathione, an enzyme then reduces this molecule. Glutathione is actually three amino acids chained together. Alpha Lipoic acid is a substrate that the reducing enzyme is attached to.

It protects the neural cells from glutamate cytotoxicity by reducing the loss of glutathione following a glutamate challenge. The glutamate challenge follows a stressful neurological event (viruses, injury, hypoxia – lack of oxygen, or general stress). It has been shown that people in chronic pain have mood alterations due to the fact that the constant firing of the pain receptors in the brain cause a glutamate challenge to the mood centers and that these neurons are actually dying off from the damage.

A good daily dosage is between 50 – 250mg daily, possibly more during challenged times.
Pycnogenol – Or better yet oligophenolic compounds (OPC)– Oh yea the latest and greatest in the antioxidant shuffle. This is derived from the Pinus maritima tree of the french coast. In this same class is grape seed extract and other pine tree extracts. What one has to be careful here is the extraction method. If chemical solvents are used then some of the antioxidant properties are lost, this and heat can dilute the properties.

Silica hydride - I have a dedicated section just for this wonder of modern science. You can find it under the Microhydrin link.

Others - this category includes bioflavenoids, proanthocyanidins, esters, etc. It is best to do some research on whatever ingredient is contained within your antioxidant compound before using. I suggest Medline. The Medline database contains a very comprehensive list of abstracts culled from journals from all over the world and is your best bet to get the latest info. If you want the complete article you'll have to chum up to a library that has the Loansome Doc agreement with the Medline folks. Warning, this type of reading is dry and difficult without some chemistry, biology, or physiology background, but it is manageable.


Conclusion

As scientists discover more about the human body and it's associated biochemistry, we will undoubtedly come across more antioxidants and soon discover that we need more and more of these cofactors in order to prevent a whole host of deleterious effects from aging, the environment and disease. These are exciting times and we, as homeopaths, have yet another tool in our case to help with the stressful times our clients are undergoing. I suggest that in any compromised client that you start off low and slowly work up, for if you go in too strong a backlash of "die off" or the Herxheimer effect will unsettle your client. Also I always forewarn the client that they will indeed become ill during the detox regimen. As Homeopaths we are keenly aware of this revisit effect with the unraveling of layers of disease, stress and trauma.

Good luck in your gentle healing arts.

1. Bruice, PK; Organic Chemistry, second edition; Prentice-Hall, NJ 1998

2."Coenzyme Q10, a cutaneous antioxidant and energizer." Hoppe U, Bergemann J, Diembeck W, Ennen J, Gohla S, Harris I, Jacob J, Kielholz J, Mei W, Pollet D,Schachtschabel D, Sauermann G, Schreiner V, Stab F, Steckel F; Paul Gerson Unna Research Center, Beiersdorf AG, Hamburg, Germany.

3. "Bioenergetic effect of liposomal coenzyme Q10 on myocardial ischemia" reperfusion injury. Niibori K, Wroblewski KP, Yokoyama H, Crestanello JA, Whitman GJ Department of Cardiothoracic Surgery, Allegheny University/MCP, Philadelphia, PA 19129, USA.