oxidation

Traumatic Brain Injury and Oxygen: Understanding the Role of Free Radicals

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In using a fictitious example, the mother of a football playing athlete takes an interest in a head injury sustained by her son. Perhaps she wanted to know why he developed certain symptoms and what sort of treatment might be helpful. Doing her own research, she has been confronted with a mysterious, often repeated, discussion about “free oxygen radicals” in the brain in relation to head injury. This post may hopefully take some of the mystery out of the discussion and even suggest a means of prevention.

Burning a Fuel Is Oxidation

The chemistry of energy metabolism as it affects the brain/body is exceedingly complex. However, in order to illustrate the principles of oxidation (burning) perhaps, it can be seen in the simplest terms by recognizing what happens when we burn (or oxidize) something such as a sheet of paper. The paper does not ignite spontaneously: some form of energy has to set it alight. When we strike a match, energy is consumed by the arm and hand of the person that does the striking. This energy is used to move the match against a rough surface and the friction causes heat energy to arise and light the match. Energy is required for each step. Having applied the flame from the match to the newspaper, we have transferred the energy and the match is incompletely burned. In each case, the match and the paper act as fuel, and the heat energy released is produced by the fuel combining with oxygen. Because of incomplete combustion, both the paper and the match are converted into ash, the leftover unburned portions.

Speed of the Oxidation

In this simple case, the heat energy is released into the atmosphere and disperses. The energy cannot be used to perform work. The same thing happens with an open fire but there is an additional factor. For example, if we blow on it, the fire burns more briskly. Sparks are produced that may set fire to the surrounding dead grass. Energy has to be captured and controlled to do work. Any form of burning, combustion, fire, or singeing (we have many words for the process) is produced by a fuel combining with oxygen. The resultant energy is used to do work. Combustion is never complete; some form of ash is left over.

In the body, we burn glucose and the term used is oxidation. The “ash” is carbon dioxide and water, both of which are partially lost in the breath.  It is the speed of the reaction that makes a difference in the rate of energy production. Singeing is a very slow combination of the material with oxygen whereas an explosion is an extremely fast reaction. Neither of them could function without oxygen. The production of sparks from an open fire may be used as an analogy for free oxygen radicals. This part of the post may be overkill, but I am discussing everyday phenomena that are frequently taken for granted.  Little or no thought is generally given to the mechanisms involved.

What Are Free Oxygen Radicals?

I have already compared them with sparks from an open fire. This means that oxidation in the body can be slow or fast and the speed of the reaction has to be controlled. Too little oxygen is as bad as too much, encapsulated as “all things in moderation”, arguably the most important philosophical annotation that has ever been conceived, since it applies to everything.

As already indicated, glucose is the major fuel of the body, particularly for the brain. The oxidation of glucose is mediated through a series of vitally important enzymes, yielding energy that is stored in the cell as a chemical substance known as ATP (adenosine triphosphate). An inexact analogy would be that a head injury acts as a form of stress that requires a vast amount of energy consumption to adapt to the injury. The rapid oxidation that follows gives rise to free oxygen radicals that are the equivalent of sparks in a vigorously burning fire. The “sparks” are thrown out of the “fireplace” in the cell and “set fire” (oxidize) to surrounding tissues, thus causing the damage. It is often difficult for people to understand that the energy required to give rise to mental and physical function is from a form of combustion induced by chemical reactions. The chemical energy has to be transduced to electrical and is the reason why we can measure the activity of a given organ such as the heart by the electrocardiogram and the brain by the electroencephalogram.

Note that oxidation does not occur spontaneously. The glucose must be “ignited” and vitamins are the equivalent of a match. Although it is a poor analogy, vitamins liberate and transfer energy. It is of course extremely important to recognize that energy is something that we cannot perceive in any way except by its effects. We cannot see heat energy but we can feel its effects. We cannot perceive the energy that drives the brain although we can appreciate the thoughts that arise from its consumption.

When we eat food it becomes the fuel that has to be oxidized, releasing chemical energy. That chemical energy has to be transduced to electrical energy to drive function. It must be stated that our bodies are constructed according to a code known as DNA. If that is imperfect, we may have “a genetic effect” responsible for disease. In addition, if the food does not contain the right fuel or does not contain the factors that ignite it, the effect is disease. The central figure is energy. Symptoms are sensory effects in the brain that indicate that “something is wrong (for example) in your left elbow”. Pain is felt in the brain, not the part of the body with inflammation. A genetic error may not initiate disease by itself. It often requires nutrient deficiency and/or some kind of stress such as an infection, trauma, or prolonged mental stress. Any one of these requires increased energy expenditure to adapt to the stress, in much the same way that a car uses more energy derived from fuel consumption when climbing a hill.

Traumatic Brain Injury

Traumatic brain injury is a significant cause of death and disability. The primary impact causes initial tissue damage which initiates biochemical cascades known as secondary injury. Free radicals are implicated as major contributors to secondary injury. Another manuscript reports a study on rats. These authors induced thiamine deficiency and found that there was an increase in free radicals in the brain. Exercise stresses body chemistry that depends on thiamine, riboflavin, and vitamin B-6. The requirements for these vitamins may be increased in active individuals, particularly athletes. Biochemical evidence of these deficiencies in active individuals has been reported, but studies examining these issues are limited and equivocal. There are no metabolic studies that have compared thiamine status in active and sedentary persons. These authors state that exercise appears to decrease nutrient status even further in active individuals with pre-existing marginal vitamin intakes or marginal body stores. Thus, active individuals who make poor dietary choices are at greater risk.

The ability of humans to respond to stresses, such as altitude, heat, trauma, surgery, or infection can be influenced by nutritional status. Hans Selye is the most famous scientist who studied the effects of physical stress on animals. He came to the conclusion that energy was necessary for the animal to meet the demands (adapt) imposed by any form of stress and that it was energy failure that was responsible for the animal’s collapse. He formulated the idea that chronic human diseases were the “diseases of adaptation”, implying energy insufficiency as the underlying cause. This suggests that the acute phase of an infection is the defensive, adaptive reaction that requires nutritional perfection to supply the energy.

Protection Versus Treatment

Currently, the only method to try to prevent brain injury in athletes is protective equipment and the statistics indicate that this does not seem to be very effective. That nutritional elements might have a protective effect on brain injury might seem like an absurd disconnect. We have repeatedly emphasized on this website that food choices are poor in the modern world. The diet for many people is laced with empty calories that challenge and overwhelm the mechanisms that govern oxidation. The vitamin content may be adequate for a well-chosen diet of natural foods but inadequate in relation to the empty calories, a state that is commonly present in young people in particular. We are well aware that measuring the concentration of thiamine in the blood, the usual and customary practice of attempting to identify thiamine deficiency is usually perfectly normal in mild to moderate deficiency. If our resolute hedonism causes us to continue making poor choices, perhaps it would make sense to add vitamins as supplements, an idea that has been castigated many times in published statements. This is because it is widely believed that “vitamin deficiency” in an advanced country like America is nonexistent. Finally, I must say something about treatment. There is some evidence that intravenous infusion of water-soluble vitamins given to an athlete that suffers from the symptoms of brain injury can be at least partially relieved. This is basically because these vitamins play a vital part in controlling the use of oxygen in cellular function. Without understanding these basic mechanisms, the use of intravenous vitamins to treat brain injury would be incomprehensible.

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This article was published originally on June 7, 2018. 

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Oxygenation, Nutrition and Cancer

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One of the most important scientists in medical research was Otto Warburg whose presentation at the 1966 Nobel Laureate conference in Lindau, Germany, was entitled “The Prime Cause and Prevention of Cancer”. Based on his meticulous experiments and independently verified thousands of times, Dr. Otto Warburg knew the prime cause of cancer. What he discovered was that oxygenation of our body cells is the key issue. A normal cell derives the energy that it uses for function by a complex series of biochemical reactions that yield energy. The normal use of oxygen results in respiration, also known as oxidation, something that takes place in the nucleus of the cell. If there is a deficiency of oxidation within the cell, energy production is by fermentation, a less efficient way of producing energy. The resulting energy deficit may be the underlying cause of the sensation that we call fatigue, as well as affecting the structure and functions of the cell that influences the process of becoming cancerous. Once a cell has become cancerous, there is no way to return it back to its normal functioning. It must be destroyed. So the key is to kill existing cancerous cells while preventing new cancerous cells from developing. It is the long term deficit over years that finally erupts as cancer and a salient preventive measure is appropriate nutrition.

Oxygenation: Key to Health or Disease

The major message is that the normal delivery of oxygen and its use in respiration within cells is vital to complete health, resting heavily on the pioneering work of Dr. Otto Warburg. Most of us give little thought to what we do with the oxygen that we extract from the air by breathing. We are aware, of course, that oxygen is picked up by the hemoglobin in our red blood cells. The action demands an intricate biochemical transfer of oxygen from the lung alveoli to those cells. They then travel in the blood stream to all our body tissues and another complex reaction transfers oxygen from the red blood cells to the cells that make up all our tissues and body organs. This transfer mechanism depends on the health of the cell membrane that is at least partly dependent on the ingestion of the vital omega-6 and omega-3 polyunsaturated fatty acids (PUFAS).

Our cells, and we have between 70 and 100 trillion of them, have an extraordinarily complex structure. Each one, with the exception of red blood cells, has a nucleus, surrounded by a fluid called cytosol. The outer membrane of each cell, known as the plasma membrane, represents a potential barrier to the transfer of nutrients, including oxygen, from red blood cells to the cytosol. Oxygen, vitamins, and essential minerals then have to cross the membrane around the nucleus where respiration gives rise to an energy storage molecule called adenosine triphosphate (ATP). If this transfer is not complete, respiration declines and the cell uses fermentation in the cytosol to synthesize ATP.

This essential transfer across membranes depends on what is known as fluidity. The nearest that we can get to describing cell membrane function simply is that they require fluidity similar to the fluidity in a soap bubble, but much more complicated. Omega-6 and omega-3 PUFAS are essential oils obtained from ideal nutrition and they help in maintaining this fluidity, enabling oxygen transfer and absorption of cell nutrients to take place.

tumor hypoxia

Oxygen, the primary nutrient, then has to be consumed in the process of synthesizing ATP. It is, of course, useless to have oxygen transferred into cells if it then remains unused. The fuel that is burned (oxidation results from the combination of oxygen with a fuel) in this process is glucose and one of the vital components is vitamin B1 (thiamine), a nutrient that I have emphasized repeatedly on this forum. Deficiency of this vitamin, together with an excess of simple carbohydrate, causes the ancient scourge of beriberi.

One of the known factors in this disease was reported by Japanese investigators many years ago. They found that the oxygen saturation of arterial blood (on route to body tissues) in beriberi victims was very low. The venous oxygen saturation was very high (blood returning to the lungs for oxygenation). This means that the pickup of oxygen at the lung was poor and it was transferred to the venous circulation without doing its job in the cells. It is therefore possible that long term, low grade thiamine deficiency could well be the forerunner of cancer.

Thiamine, Cancer, Diabetes and Neurodegeneration

Recently it has been found that low dose administration of thiamine stimulates cancer cells in an animal model, while very high doses inhibit their growth. Diabetes type I is pancreatic insulin deficiency. Type II is insulin resistance. Alzheimer disease is associated with glucose metabolism and may be diabetes type III. Cancer may turn out to be diabetes type IV. Reading  between the lines, it looks as though thiamine metabolism is a key factor in causing many diseases  because of its role in oxidation. This information is also important in understanding why malnutrition, particularly involving an excess of sugar, as is common today, is causing so much functional change in millions of people.

The so-called psychosomatic symptoms are often due to the early stages of beriberi, a disease where changes in the control mechanisms of the autonomic nervous system have long been known to occur. Thus the reduction of normal oxygenation and oxidation in the production of cancer is emphasized and it may well be that we can extend the principle to the cause of many different diseases. The brain is the most oxygen consuming organ in the body so that even minor deficiencies of oxidation can affect its performance. Since the lower brain contains the mechanisms of automatic control of the autonomic endocrine axis, it could explain why so many publications in the medical literature report an association of autonomic nervous system dysfunction with a variety of organic diseases that are so common in our world today.

Considering Malnutrition in the Presence of Abundance

A little history may help us to understand why various forms of malnutrition are so easy to neglect when we fail to follow the rules set by Mother Nature. Beriberi often broke out in Japan when there was increased affluence. The reason was really quite simple. Brown rice is the full grain and the vitamins needed for processing the starch are stored in the cusps around the grain. White rice is produced by milling the cusps off the grain and this was performed at a rice mill, a relatively expensive procedure for many people. The cusps were given to feed pigs and it is paradoxical that the pigs were better fed than the humans. White rice was therefore considered to be a marker of affluence and caused many people to set the milled rice in a silver bowl and invite their friends to dinner. They did not realize that they were inducing the common dread illness that they all knew about.

Can we take a leaf out of their book and compare our affluence of today with what happened in Japan years ago? Sugar and simple carbohydrate are dangerous commodities that may well be one of the commonest causes of disease in Western civilization. Consider this together with the absence of appropriate PUFAS and other essential  nutrients and we cannot deny that malnutrition is today very much alive and well.

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