INSIGHTS INTO THE REALM OF FREE RADICALS
When I was a boy, I sometimes accompanied my father, who in his capacity as alpinist and banker was also the SAT (Tridentine Alpine Asscociation) refuge administrator, to settle, as he would put it, the end of season accounts, before the close of the winter season. In those days, the money for the skiing station managers was carried in a canvas haversack, and we would take the bus to a certain point, and then proceed on foot, sometimes as far as the Carlo Alberto. But that was in the early ’50s, and I was in my “early fifteens”, i.e. fifteen or thereabouts. My father also had to assess the infrastructure for damage, and say what needed repairing or replacing. I recall that he had a strange way of speaking about the corrosion of the metal structures, which was possibly his way of making himself understood. He would say: “you see, apart from the snow and the rain, the metal dies first in the refuges lower down, and later higher up.” Attributing life and death to roofs and guttering as if they were living things is something I would later associate with people, especially the great Methuselahs of the mountains, who lived longer in a climate that was less oxidising, or less oxygenated.
The unusual title of this piece came out of my long-since oxidised files.
Having made this anecdotal premise, I wish to highlight the fact that often words enter into the common language perfectly legitimately, but then cease to be understood; we use words without knowing what they mean beyond mere simplification. One banal Example: if I asked you the difference between belonging and dependency, I doubt that many of you would be able to answer correctly and concisely. This is all the more true for technical and scientific terminology. The preamble serves to justify the preface, which leads us into redox and free radicals, today’s topic. I will conclude this part by saying that in presenting the topic we are faced with a very modern and paradoxical difficulty, which stands in direct opposition to the difficulty we had in my day: that of getting rid of the superabundance of information and presenting only what is important.
Let’s start with oxygen. Life and death are connected with oxygen; as they say in Tibet that the devil is God’s shadow, but then God is clearly also the devil’s shadow. Oxygen is the two-way transmission link between two physical models, living and non-living matter.
The symbol of oxygen is O, its atomic number is 8, its atomic weight is 16. It has 6 electrons in its external orbit, two of which unpaired due to their having the same “spin-up” rate (a rotation movement which, if you don’t want to, we need not speak about). It is without colour smell or flavour. It should account for one-fifth of the volume of air. It constitutes 88.8% of the weight of water, around 50% of the weight of the Earth’s rocks, and it combines with almost all elements to produce oxides and anhydrides. For the record, an oxide consists of an element+oxygen, whereas anhydrides are oxides that react with water to produce acids. For future reference: rapid combination with the influence of light and heat leads to combustion, whereas if it is slow it leads to oxidation. The difference lies primarily in the affinity between the reagent substance and the concentration of oxygen.
However, here we shall take hydrogen as our atomic model, because it is the simplest. Like all atoms, it has a nucleus charged with positive electricity known as proton (there are also neutrons), and a periphery Charged with negative electricity known as electron, which is in constant movement. And there is balance.
Chemical properties depend on electrons. Indeed, it is through their external orbits that atoms tend to connect with each other to form matter. In the process of ionisation, or creation of ions, we can distinguish positive ions in which the hydrogen atom loses its electron and becomes a proton, and negative ions in which an atom gains one or more electrons. As mentioned, atoms connect by means of their external orbits to form molecules and then matter, or aggregates of molecules. During electrolysis, the decomposition of an electrolyte (composite conductive liquid) due to the passage of electricity, ionic dissociation occurs, in which the negative ion gravitates to the anode and the positive ion to the cathode. The passage of electricity occurs by means of the circulation of the ions. The anode is a receptor for negative ions, whereas the cathode is a donor of positive ions. The positive ions mentioned earlier, the protons, are micromagnets that generate electromagnetic fields.
In water, H2O, the acid element is provided by the H+ hydrogen ions, whereas the base element, or oxyl ion, is provided by OH-. With more H+ elements there is a high hydrogen potential. Likewise, with more OH-, there is a lower hydrogen potential. That is how PH metres work. Once an ionic balance has been reached, the liquid medium will contain other electrons which can be measured with a third electrode. This potential is called reduction-oxidation potential, or redox; it is expressed in millivolts as potential reducing or oxidising force.
The phenomenon is crucial to all vital processes, since water is clearly the predominant medium. Thus, H2O = water, H2O+C+N = proteins, H2O+C = carbohydrates, or glucides.
As my teacher, L.C. Vincent, the inventor of bioelectronics, used to say, the electron-hungry female absorbs the male’s hypernegative seed. But that belongs to my French past.
Oxidation and reduction are therefore inseparable, and the phenomenon is connected with a transfer of electrons. Summing up, we might say that a solution that acquires electrons reduces, whereas one that loses them oxidises and forms molecular oxygen. You cannot have only reduction or only oxidation.
In living organisms, redox reactions are catalysed by enzymes known as oxidoreductases with a transfer of electrons from an electron donor, an oxidising reducer, to an oxidised acceptor molecule, which is reduced. For example, in breathing, electrons in the form of hydrogen ions move towards a series of transporters, ultimately combining with molecular oxygen. Biological oxidation passes through gradients of potential; in other words, the movement is towards compounds with increasingly positive redox potential, whereas, by giving up electrons, high energy biological molecules are broken down into smaller molecules.
Therefore, with oxidation (catabolism), energy is released by means of fission, or the splitting of larger molecules into smaller ones. The energy thus released is accumulated as ATP (adenosine triphosphate). On the other hand, in the construction of new molecules, or fusion, smaller molecules form larger molecules (e.g. aminoacids for making proteins) with the consumption of ATP. The process is called anabolism.
According to the great Otto Warburg, cancer ultimately consists of the replacement of the aerobic breathing chain mentioned above with an anaerobic one in which the end acceptor is not oxygen but lactate.
It is clear, therefore, that the concept is closely linked to pH and redox. A third value, which I will not speak about, is conductance or resistitvity. However, we speak of neutrality when there is balance between reducing force and oxidising force (28 mV). It is also clear that balance signifies lack of movement or ionic migration, and that oxidisation is a form of stagnation in vital processes due to the loss of electrons. Lack of movement, lack of desire, the driving force behind the dance of opposites, as the Veda taught some years ago, somewhat before everybody started speaking about antioxidants. We can see, therefore, that a low alkaline pH (venous) and a reducing solution corresponds to life, whereas a markedly alkaline pH and an oxidised solution corresponds to death by stasis: life is only movement. If you think about it, the dead frighten us because of their absolute immobility. For example: enzymes are active with pH 7 or less and increasingly inactive with an alkaline pH. Draw your own conclusions even from looking only at enzymes. Enzymes catalyse and speed up redox reactions.
Consider that a venous pH should ideally be – although personally never found – +/- 7,30 (slightly alkaline), and the redox ration between 22 and 25 mV, expressed as rH2.
The causes of diminished hematic pH are:
Certain endocrine disturbances, unbalanced nutrition, alterations in the functioning of the liver, violent physical exercise, convulsions, shock, insulin-induced hypoglycaemia, advanced salicylic intoxication, methanol intoxication, ingestion of ammonium chloride or calcium
chloride, diarrhoea, Addison disease, renal tubular failure, alcohol, barbiturates, carbon dioxide, morphine, surgical anaesthetics, asphyxia, emphysema, hypoventilation, certain types of heart disease, certain skeletal-muscular diseases.
The causes of increased hematic pH:
Vomiting, gastric irrigation, potassium deficiency, ingestion of sulphates, phosphates, nitrates, chloride depletion, insufficient introduction or assimilation of potassium, widespread burns, steroids, diuretics, laxatives, barium enemas, ultraviolet treatment, radiation therapy, neural diseases, the initial stages of salicylic acid therapy, sulphamides, quinine, fever, high ambient or atmospheric temperature, hepatic coma, gram-negative bacteremia.
Obviously, there are many more factors besides, but this is not a lesson in bioelectronics. What is clear, however, is the implication for our dietary regimens. For instance, it is clear that we should eat life, not death. Those who eat death are preparing their own death. Remember that fire has featured in the history of man – man the crudivore, who has enabled us to be here today eating tamasic food, the fool’s food, as defined by the Ayurveda – for only a few thousand years. Or, if this is too much for you, the biostatic (as opposed to biogenic, i.e. that generates life) food that is so popular in this homologated civilisation of ours. If you are still unconvinced, just look at the rise of hyperoxidised alkaline-based diseases, such as cancer, thrombosis, viral diseases, expansive neuroses, etc. etc., which thrive in these conditions alongside senility, which is not ageing, but a negative added value of decay.
I have made this brief excursion into bioelectronics so that certain points be made clear:
1) the importance of pH in redox processes;
2) redox itself depends (in biological electrolysis) on the persistence, or not, of electrons once the ionic balance has been achieved;
3) the fact that hyperoxidation is the enemy to defeat and antioxidants are the allies we do not turn to often enough. Less money, more electrons, we might say. I would go further and say that the accumulation of the former works contrary to the acquisition of the latter. Suicidal entropy, in other words;
4) the inseparable connection between free radicals and the reduction-oxidation processes required by life;
5) by means of redox, free radicals are at the forefront not only of theories about ageing, but also in degenerative disease research, including cancer, arteriosclerosis and neurocompetent diseases.
Definition: a free radical can be described as a fragment of molecule with an atom that has an orbital occupied by one single electron, or unpaired electron, or two electrons defined as parallel. The most evident characteristic of free radicals is their extreme responsiveness to attempts to establish a balance. They are called free because they are capable of independent life,even if their life is measured by a fraction of a second. In living matter, generally in the process of electron transfer, they act in cellular metabolic processes. They are produced in large quantities not only in phosphorylation processes, but also in ionising radiation and drug metabolism. In inflammation, especially when chronic, leukocytes produce large quantities of free radicals. In autoimmune diseases, the weapons of the immune system, such as hypochlorous acid, also a free radical, are turned against the body itself. And so on. To sum up, heat, luminous and ionising radiation, processes of synthesisation, oxidation, electron transfer, drug metabolism, inflammation and immune defence responses all necessarily lead to the production of free radicals.
As mentioned earlier, oxygen has two unpaired electrons in its external orbit and is therefore to be considered a double free radical, with double the appetite for electrons. Oxygen is therefore poisonous. Its double appetite robs other molecules of electrons, making them in turn unstable and bulimic, by means of a chain effect. The damage affects proteins with the DNA, cellular membranes and those vitally important power stations in the cell that are the mitochondria, where the phosphorylation processes of the respiratory chain take place.
Naturally we also possess deactivating defence mechanisms (e.g. thiols, which oxidise easily), electron donors (superoxidodismutases, catalases, ascorbic acid, carotenoids, vitamin E, melatonin, etc.), scavengers that eliminate damaged DNA and DNA repairers. The immune system also uses free radicals as artillery against invaders, which, thankfully, are also vulnerable (to the advantage of free radicals in getting rid of them).
Unfortunately in this case, as often happens in war, the allies cause damage similar to that of the enemy. Another example: macrophages are avid consumers of oxidised products, and activating them means increasing their appetite, as well as encouraging them to secrete messengers for other components of the immune system.
Stress deserves a mention here, as it produces free radicals not only as a by-product of the energy used, but also from the hormones involved in the stress, which in turn become free radicals.
The destruction caused by the search for a balance is called oxidative stress, and for every increase in the quantities of energy used, or at least in the combustion, the number of free radicals also increases.
The work of each cell produces around twenty thousand free radicals per day. You can amuse yourselves by multiplying that by +/- 60 trillion cells.
The main free radicals are:
1) superoxide (O2), which has captured an electron and can transform into other free radicals;
2) lipoperoxide, when an electron is removed from the fat protein of cell membranes (lipid peroxidation);
3) singleton, devastatingly fast;
4) hydrogen peroxide, which can generate hydroxyl;
5) hypochlorous acid, as artillery in the immune system.
Furthermore, the nitric oxide and carbon monoxide we breathe in our cities become extremely powerful free radicals when exposed to oxygen; their by-products damage cell membranes and their lipidic components, thereby forming lipoperoxides.
This triggers the oxidation of arachidonic acid and the formation of prostaglandins and leukotrienes. Neutrophiles initially, then monocytes transformed into macrophages, they produce vast numbers of free radicals to tackle the invaders, with the following implications.
As well as the damage seen above, radicals are also responsible for cross linkages between proteins, which complicate matters. Linkages are the involuntary coupling, stray coupling, of two large molecules, which leads to mutations.
Without going into details, it is worth recalling that the lipid peroxidation mentioned above in connection with damage to the cell membranes of lipoperoxide increases with hepatic lesions, drug use and the excessive assimilation of iron and copper. Low density and high cholesterol oxidised fat proteins (LDL) are metabolised more slowly and have cytotoxic effects on the cells of the vascular wall (the future arteriosclerotic plaques). Currently, in 2009, there is some radical rethinking of LDL and cholesterol generally, which appear to be anything but harmful. But this will be the topic of another blog entry [author’s note].
The anion superoxide is predominant in diseases such as lung cancer, Alzheimer’s disease, rheumatoid arthritis, hypertension, etc.
And now back to protection mechanisms.
Part of what follows can be found in the previous article, ‘Old age versus senility’.
It is clear that the processes of self-protection and self-reparation are becoming increasingly inadequate. In fact, diseases linked to the degeneration of the biological system, beginning with senility, have increased manyfold. Senility is not ageing, but decay in physiological ageing. As for longevity, as I have said elsewhere, it has not increased, rather it has decreased; what has increased is life expectancy. We die, in other words, less prematurely. Neither has happiness increased over the past two thousand years, and the connection between the two is not arbitrary.
The question remains the same: what is the cost of benefits that are surrogates of happiness and what do we pay for comfort, that meagre replacement for functional respect?
That said, since we all agree that man is not perfect, I don’t see how he can produce anything but imperfection.
But, realistically speaking, there are some things we can do:
1) Improve the quality of the relationship between natural needs (not their surrogates) and their fulfilment. In other words, the quality of life.
2) Avoid, unless there is no choice, chemical cures (let us bear in mind that a drug, in order to be a drug, must have a lethal dose, contraindications and side-effects). I won’t even mention chemotherapy which, by damaging the DNA, often leads to other forms of cancer.
3) Take a comprehensive approach to diet, something which is becoming increasingly difficult to do.
4) Since the wise men of China used to say that a cold once every ten years is too much, and we unfortunately do not belong in that category, we should resort to tried and tested natural remedies that serve to minimise the problems that are inevitably connected with living. In other words, prevention.
Protection, which can mean “increase the coverage”, is also synonymous with prevention, namely:
a) Optimise the immune response (meaning activating self/non-self recognition and strengthening our defences).
b) Use natural activators of biological and biochemical functions.
c) Encourage the elimination of toxins.
d) Make a “gift” to the body in the form of electron donor substances.
e) Give available energy to biological systems.
f) Increase the use of antioxidants, reducing the input of oxidants.
Caution: too many antioxidants (I do not refer to the ones introduced with food) are as damaging as too few.
Concerning antioxidants, it is worth noting that they were widely used in antiquity and that we have once again reinvented the wheel. Unless you are of the opinion that spices were so precious because of their fragrance alone. Smoked meat kept because smoke contains phenols, or it didn’t rot because of the polyphenols contained in nutmeg and cloves. Likewise, wine did not become vinegar with the addition of pine resin, which is rich in bioflavonoids. And so on.
Antioxidants can be roughly divided into four categories:
1) Inhibitors, which interrupt oxidation by reaction with free radicals, forming stable radicals. They are of the phenolic type.
2) Peroxide decomposers, which do not provoke other free radicals. For instance, perissosomas are oxidasic enzymes that employ molecular oxygen, neutralising free radicals and forming water and oxygen.
3) Photostabilisers, for absorbing ultraviolet rays.
4) Metallic deactivators that chelate or sequester metallic ions (for example, citric acid).
It is easy to see how, if we want to formulate and produce composite natural remedies, it is necessary to take into account the greatest possible number of protective factors and combine them with the utmost purity and harmlessness, as well as the most effective doses. It is not as easy at it seems.
A further note on terms we use without fully understanding their meaning. The word ‘Nature’, from which ‘natural’, does not have any adequate etymologies, except, in my opinion, for the relationship with status (condition). I will therefore quote St. Thomas, who defines Nature as: “the things and beings of the Universe that are sustained by their own laws and order and are subject to contemplation and study by man.” (the year was 1250). Words to conjure with.
AN UNSETTLING NOTE ON THE IMMUNE SYSTEM (2001)
Despite the fact that doctors are aware of both the growing importance of the immune system and the gradual erosion of our defences, two vital aspects are nevertheless often overlooked:
1) The direct and indirect quantification of this incremental deterioration.
2) The ability/qualifications to apply reasonable remedies.
The disinformation or professional blindness with regard to the numbers in point 1) is caused by:
a) The legitimisation of immunosuppressive “therapies” (cortizone, chemotherapy, radiation, antibiotics, invasive examinations, etc.), even when not necessary. The consequence is perforce that the price to pay is not seen. This avoids the responsibilities that come with knowledge.
b) The ‘convenient’ lack of available information from the monitoring of the growing levels of decay.
c) The consistently “convenient” superficiality with regard to observable data, even when there is no need for information.
d) The mental anaesthesia that derives from getting used to the declining efficiency of the immune system.
Point two is a logical consequence of the first, and therefore its corollary.
It is also to be noted that even those who would deny all of the above with their efforts are nevertheless subjected to the negligence of others. I believe that the readers of these notes belong to the category of the damaged (when not victims).
Real prevention, let alone therapies that cannot be patented, are not of interest. The biggest “business” is not weapons, but disease, or to be more precise, cancer.
Some data on the progressive damage to our defences, albeit unfortunately not up-to-date.
1961 – Levinson, McFait – report on laboratory diagnostics and techniques
Normal values of lymphocytes: 20-30%
1967 – Roversi (Farmitalia)
Normal values of lymphocytes: 25-33%
2001 – Hospitals generally
Normal values of lymphocytes: 18-49%
Obviously, given the times, I don’t have data for the subpopulation of lymphocytes; and it’s lucky that I don’t, because it would be an eye-opener. We do know, however, that NKs (Natural Killers, similar to lymphocytes), which do not need previous encounters with the enemy in order to attack, have reduced their numbers by 30% in the last 15 years. The decline has unfortunately reached the 3% per annum mark (data not updated) and is accelerating. It is needless to point out that NKs are crucial in the direct destruction of cancer cells.
The objection to the data is oviously very straightforward: measuring and techniques have improved over time. True. But it is hard to believe that the abnormal data regarding lymphocytes and Natural Killers are the result of modernity.
How many other bitter surprises would we have if we could have access to a good archaeology of the immune system?
However, it is not necessary; you just need to analyse the type of diseases we have, the lymphcytosis and the decline of NKs – which is clear for all to see – to understand that we are small weak convalescents with a chronic condition. Like the children I sent away to the seaside in the ’60s, when lymphocytes were above 30%, or the tubercolosis sufferers just out from the sanatorium and under constant surveillance. It is the era of small fevers and asthenia, depression and panic attacks, autoimmune disease and “chronic fatigue syndrome”. The fatigue of living, you understand.
I wish to conlcude by highlighting what is evident today, that is the rise of:
- autoimmune diseases
- chronic diseases
- stress-related diseases
- thyroid-related pathologies
- precocious senility-related diseases
- “nervous diseases”
But neither do I wish to go on.
These conditions are all closely linked to the immune system, which is struggling to say the least, even without considering the tables and lab data.
I know, perhaps it would be better to ignore the problem, avoid unnecessary effort; and hope to get away with (our children too?). But it is only a hope; the last to die, precociously, with us. As long as we don’t complain, though.
Dott. Glauco Smadelli