What allows us to live and our bodies to function are billions of chemical reactions in the body, which occur every second. These are essential for the production of energy, which drives all the processes of life, such as nervous function, movement, heart function, digestion and so on. If all these enzyme reactions invariably occurred perfectly, there would be no need for an antioxidant system. However, even our own enzyme systems make mistakes and the process of producing energy in mitochondria is highly active. When mistakes occur, free radicals are produced. Essentially, a free radical is a molecule with an unpaired electron, it is highly reactive and to stabilise its own structure, it will literally stick on to anything. That "anything" could be a cell membrane, a protein, a fat, a piece of DNA, or whatever. In sticking onto "something", it denatures that "something" so that it has to be replaced. So having free radicals is extremely damaging to the body and therefore the body has evolved a system to mop up these free radicals before they have a chance to do such damage and this is called our antioxidant system.
Free radicals come from inside the body (mitochondrial energy production, the P450 detox system in the liver and immune activity from inflammation) and from outside the body (poisoning from pesticides, volatile organic compounds, heavy metals, radiation etc)
In recent years even more stress has been placed on our antioxidant system because we are increasingly exposed to internal toxins (modern diets) and external toxins (pollution), which often exert their malign influence by producing free radicals. Therefore, it is even more important than ever to ensure good antioxidant status.
Free radicals effectively accelerate the normal ageing process whilst antioxidants slow the normal ageing process. The best example that we have all seen is the effects of smoking - cigarette smoking produces large amounts of free radicals and people who have smoked for many years have prematurely aged skin. Smokers also die younger from cancer or arterial disease - problems one expects to see in the elderly. Conversely, people who live and eat in a healthy way age more slowly.
The normal antioxidant system
There are many substances in the body which act as antioxidants, but the three most important frontline antioxidants are
- Co-enzyme Q10. This is the most important antioxidant inside mitochondria and also a vital molecule in oxidative phosphorylation. Co-Q10 deficiency may also cause oxidative phosphorylation to go slow because it is the most important receiver and donor of electrons in oxidative phosphorylation. People with low levels of Co-Q10 have low levels of energy.
- superoxide dismutase (SODase) is the most important super oxide scavenger in muscles (zinc and copper SODase inside cells, manganese SODase inside mitochondria and zinc and copper extracellular SODase outside cells) , and
- glutathione peroxidase. This enzyme is dependent on selenium and glutathione, a 3 amino acid polypeptide, and a vital free radical scavenger in the blood stream.
These molecules are present in parts of a million and are in the frontline process of absorbing free radicals. When they absorb an electron from a free radical both the free radical and the antioxidant are effectively neutralised, but the anti-oxidants re-activate themselves by passing that electron back to second line antioxidants such as vitamins A and beta carotene, some of the B vitamins, vitamin D, vitamin E, vitamin K and probably many others. These are present in parts per thousand. Again, these are neutralised by accepting an electron, but that is then passed back to the ultimate repository of electrons, namely vitamin C, which is present in higher concentrations. Most mammals can make their own vitamin C, but humans, fruit bats and guinea pigs are unable to do so. They have to get theirs from the diet and Linus Pauling, the world authority on vitamin C, reckons we need vitamin C in gram doses everyday. I recommend a minimum of 2 grams of vitamin C daily and for some patients up to six grams. Pauling himself advocated larger doses. Government recommended intake of 30 mg a day is just sufficient to prevent scurvy, but insufficient for optimal biochemical function.
Paraoxonase is an antioxidant that sits on good cholesterol (HDL) and protects this and the bad cholesterol (LDL) from oxidation. Levels of paraoxonase are determined genetically. This enzyme detoxifies organophosphate pesticides so, if deficient, this makes the organophosphate very much more toxic. It is deficient in about one third of the population and this explains why about one third of those farmers exposed to organophosphates become ill.
There are many other antioxidants present in vegetables, nuts, seeds and fruits which the body takes advantage of when they are present in the diet. Other substances such as melatonin also have profound antioxidant properties.
Vitamin B12 is an excellent antioxidant and if I have a patient with particularly poor antioxidant status then I often recommend B12 by injection. Effectively this provides instant antioxidant cover and protects the patient from further damage whilst they take the necessary micro-nutrients to heal and repair their own antioxidant system.
Have I got a problem with poor antioxidant status?
All the above antioxidants can be measured and I now almost routinely measure the frontline antioxidants, i.e. Co-enzyme Q10, superoxide dismutase(SODase) and glutathione peroxidase.
- Co-enzyme Q10 My experience is that levels in CFS sufferers are almost always down and that they can be corrected by taking Co-enzyme Q10 300mg daily for three months, after which continue with a maintenance dose of 100mg.
- Superoxide dismutase (SODase). Deficiency can explain muscle pain and easy fatigability in some patients. SODase is dependent on copper, manganese and zinc and I would expect this to be maintained in people taking my physiological mix of minerals (Mineral Mix see Mineral Mix). However, when there is a deficiency, these minerals are taken separately. Experience shows that the best results are achieved by copper 1 mg in the morning, manganese 3 mg midday and zinc 30 mg at night. Low dose SODase may also result from gene blockages and these are also looked at when the SODase test is done. Blockages are most often caused by toxic stress, such as heavy metals and pesticides.
- Glutathione peroxidase (GSH-Px). This is made up of glutathione, combined with selenium. There is a particular demand in the body for glutathione. Not only is it required for GSH-Px, which is an important frontline antioxidant, but it is also required for the process of detoxification. Glutathione conjugation is a major route for excreting xenobiotics. This means that if there are demands in one department, then there may be depletions in another, so if there is excessive free radical stress, glutathione will be used up and therefore less will be available for detoxification and vice versa. Of course, in patients with chemical poisoning or other such xenobiotic stress, there will be problems in both departments, so it is very common to find deficiencies in glutathione: If there is a deficiency of GSH-Px, then I recommend that patients eat a high protein diet (which contains amino acids for endogenous synthesis of glutathione), take a glutathione supplement 250mg daily, together with selenium 200mcg daily (which is present in my physiological Mineral Mix).
- Antioxidant status profile
- Co-enzyme Q10
- SODase (superoxide dismutase) studies
- Glutathione peroxidase
- Ketogenic diet - the practical details
- My book The PK Cookbook - Go Paleo-ketogenic and get the best of both worlds.
- Nutritional Supplements
- Mineral Mix
- Wikipedia:Free-Radical Theory
- Damage-Based Theories of Aging Includes a discussion of the free radical theory of aging.
- Superoxide dismutase page in Wikipedia
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