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From the Journal of Applied Nutrition, 1973


Response of Peripheral and Central Nerve Pathology to Mega-Doses of the Vitamin B-Complex and Other Metabolites
by Frederich R. Klenner, BS, MS, MD

The protocol of how to effectively treat Multiple Sclerosis, by Frederich R. Klenner. (In two parts, as originally published in 1973.)

 
 

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These physiological processes battling fatigue, as enumerated, are such that the sudden expenditure of a large part of the potential energy of the muscle, by the conversion of glycogen to lactic acid, does not mean a permanent loss of glycogen capital. This is so because one-fifth of the lactic acid produced is subsequently, completely combusted. Paradoxically, this re-yields energy which is sufficient to convert four-fifths of the lactic acid produced back to glycogen. The grade of muscle effort which an individual can endure before reaching his fatigue point is governed by his capacity for absorbing oxygen and discharging carbon dioxide during respiration. Each of us is absorbing some 200cc to 300cc of oxygen per minute. If we should suddenly start to run for a bus, or climb several flights of stairs, the amount of oxygen required might rise to 2,000cc to 3,000 cc and even 4,000cc. One liter of oxygen will remove seven grams of lactic acid. The individual who can absorb four liters of oxygen per minute can endure the production of 28 grams of lactic acid per minute by his muscular effort. This tells us that our ventilating system must be in grade A condition. Anything such as smoking, or even chronic sinusitis will have a detrimental effect on neurological diseases, and supportive treatment along these lines must also be entertained if success is the desired end point.

Mental Fatigue
There are other types of fatigue besetting humans. Mental fatigue can best be considered in the light of active and passive. Passive mental fatigue represents that type of medical syndrome which includes such symptoms and signs as "brain lag," sensations of pressure in the head, poor memory, loss of power of concentration, irritability of temper, increased reflexes, insomnia, anorexia and a general variety of aches and pains – the classical syndrome of neurasthenia. Active mental fatigue is elicited by continuous work, and is proportional to the duration and difficulty of the task performed. The effects are manifested by lessening in feeling, in tone, in output and in organic change. The organic change is small compared to that from equivalent periods of heavy muscular work. Most of this change can be attributed to the sensory-motor rather than to the neural element of the mental work. Mental performance is never perfectly continuous, but is alternated with pauses which become longer and more frequent in proportion to the length and difficulty of the task. Mental effects are accumulative in that they are transferable from one task to another in proportion to the tasks' similarity. Total sleep during a day off is not necessary, since the primary area of this phase of fatigue is the synapses which beg only diversion of interest and activity – something foreign to one's usual occupation. In this manner, the fatigued synapses can rest while others are busy.

Chemical Fatigue
Chemical fatigue represents one of the major groups of internal medicine. Passive chemical fatigue represents that group which makes itself known through body lassitude following the administration of a chemical compound. This group of compounds is represented by the soporific drugs, the analgesics, the many tranquilizers, and those which lower blood pressure. One must guard against seemingly harmless chemicals. Sodium bicarbonate, for example, is capable of rendering hemoglobin less capable of normal oxygen surrender to tissues. Sodium bicarbonate can take up as much as 70% of the available oxygen. The immediate result of this anoxia is weakness, even collapse; the remote effect is tissue breakdown. Sodium bicarbonate can mimic the action of carbon monoxide. This gas, as you know, combines with reduced hemoglobin, displacing oxygen from oxyhemoglobin to form the specific compound carboxy-hemoglobin. Proper doses of ascorbic acid will prevent or relieve this syndrome. It is good to remember that monoxide poisoning can exist from many sources other than auto exhausts. Smoke poisoning from fires is nothing other than monoxide poisoning, and carboxy-hemoglobin blood levels up to 7% have been reported in cigarette smokers. This can be serious, especially in a patient with a neurological pathology. Patients with Myasthenia Gravis and Multiple Sclerosis will not make progress if they use tobacco. There are other reasons against the use of tobacco. The hypoxic effect of carbon monoxide may act in a synergistic manner with other factors operative in ischemic heart disease, outstripping the limited coronary reserve and augmenting the production of stress-induced myocardial ischemia. (I need not remind you that adequate ascorbic acid intake will also "handle" this situation.)

Active chemical fatigue represents that type of exhaustion which results from the breakdown or inability to handle the normal physiological processes in the body. A classical example of this is Myasthenia Gravis. Before the advent of Prostigmin, Mestinon and Mytelase, all those who have had this disease have died unless favored with spontaneous remission and one special type of treatment which will be outlined later. The physostigmine class of drugs inhibit the action of cholinesterase. They also have a direct effect on muscle fibers, on neurons and on ganglion cells of the central nervous system, much like jumper cables on an automobile, or like a cardiac pacemaker. Their action is limited. Although the etiology differs markedly, Multiple Sclerosis is also the end result of an active chemical problem.

Metabolic Pathways – Carbohydrate Metabolism
From any textbook of physiology, one might read concerning the metabolic pathways. The sequence of enzyme-mediated reactions leading to formation of a particular product is known as a metabolic pathway. When dealing with glucose it is termed glycolysis. The primary function of carbohydrates in the body is to provide a source of chemical energy. The metabolic pathway for glucose degradation to carbon dioxide and water is divided into two parts:
1) Involves the breakdown of glucose to pyruvic acid or lactic acid;
2) Conversion of pyruvic acid to carbon dioxide and water in the presence of oxygen.
Whether the end product of glycolysis is pyruvic acid or lactic acid depends upon the supply of oxygen in the cell. When the oxygen supply is adequate, pyruvic acid is formed; conversely an inadequate oxygen supply will lead to lactic acid formation. These are generally referred to as aerobic and anaerobic glycolysis. Adequate oxygen can be made available not only through a high rate of gas exchange in the lungs, assuming that the pulmonary function tests are within normal limits, but also by taking 10 to 30 grams ascorbic acid by mouth every 24 hours. Oxygen from vitamin C becomes available through the loss and eventual break-up of water in the reaction of ascorbic acid to dehydroascorbic acid. We reported this chemistry in several papers dealing with the use of massive doses of vitamin C in Monoxide poisoning. Enzymes are also necessary in making the glucose reactions possible. Many pathological conditions can be traced to faulty enzyme production. This is usually due to genetic fault.

Food, regardless the kind, must be reduced to glucose if it is to be used to produce energy. We have already implied that only glucose can undergo glycolysis, which produces as one type end point, pyruvic acid. Pyruvic acid is a critical agent in Multiple Sclerosis, because it is the starting component of the Krebs Cycle. Each step in glycolysis, that is, the change in chemical structure occurring along the pathway to pyruvic acid from one molecule to the next is relatively small, but the total sequence of reactions alters the structure of glucose dramatically. Bio-chemists record that in the first glucose reaction, one of 19, the phosphate from adenosine-5-triphosphate (ATP) is transferred to glucose to form glucose-6-phosphate. In the third reaction a second molecule of adenosine-5-triphosphate (ATP) is used in the transfer of phosphate to fructose-phosphate. Two molecules of ATP, the key power source for life, being utilized in getting to fructose 1, 6-diphosphate, but eventually four molecules of ATP are formed resulting in a net gain for the cell of two Adenosine-5-triphosphate molecules. During glycolysis reaction number six, additional ATP molecules are synthesized from or by way of the coenzyme nicotinamide adenine dinucleotide plus 2 hydrogen atoms (NADH2) by the process of oxidative phosphorylation. This, however, cannot occur without oxygen since in the reaction NADH2 is reduced to NAD by transfer of the hydrogen atoms and electrons to the cytochrome system. Fortunately, adenosine-5-triphosphate (ATP) can be synthesized by direct substrate phosphorylation occurring during anaerobic glycolysis. Adenosine-5-triphosphate (ATP) provides the ionized phosphate groups that trap the intermediates within the cell and forms the intermediate structures required for the later stages of glycolysis. It is important to recognize that all the intermediates between glucose and pyruvic acid contain an ionized phosphate group and that ionized molecules are generally unable to cross the lipid barrier of a cell membrane. Once glucose has been phosphorylated, the intermediates of glycolysis are trapped within a given cell. Glucose enters the cell through a carrier-mediated facilitated-diffusion system. The amount of energy transferred to ATP is roughly 5% of the total potential of glucose. Thus, 95% of the ATP synthesized from the energy released from glucose depends upon oxygen and the oxidative phosphorylation occurring in the mitochondria. This gives us notice concerning the importance of good ventilation practices to maintain a high degree of vital capacity. It also argues for high daily intake of vitamin C.

Reversible and Irreversible Reactions
Most of the reactions of the tricarboxylic acid cycle (Krebs cycle) are reversible, but the reaction in which pyruvic acid is converted to acetyl co-enzyme A and carbon dioxide is irreversible. It is true that all chemical reactions are theoretically reversible, but some are limited to the plant kingdom. For example: Carbon dioxide and water can react to form glucose and oxygen, reversing the reaction which led to the breakdown of glucose, but to make it work in this reverse direction, the same amount of energy (685kcal) released during glucose glycolysis must be returned to the molecules of carbon dioxide and water. This actually happens, as you know, in plant cells through a process called photosynthesis, where the energy is obtained from sunlight. Pyruvic acid, which comes from phosphenolpyruvate, the last step in glycolysis, and which cannot be reversed once acted upon by coenzyme A to form acetyl coenzyme A, can be produced by direct decarboxylation of oxalacetic acid. Pyruvic acid from this source can be phosphorylated in the presence of ATP to form phosphopyruvate, and this can then serve as a direct precursor of the hexoses and glycogen by the reversal of the glycolytic system. Pyruvic acid (plus CO2), according to Ochoa, can be "shuttled" into the Krebs cycle through malic acid when this compound is reversibly oxidized and decarboxylated using triphosphopyridine nucleotide (TPN) as hydrogen acceptor, and catalyzed by malic enzyme. We mention these chemical routes for pyruvic acid since it plays a very important part in Myasthenia Gravis. The reversibility of the decarboxylation reactions in the Krebs cycle enhances the importance of the mechanism of CO2 fixation by animal tissues. CO2 fixation implies the utilization of carbon dioxide for metabolic purposes. As noted in any text of physiological chemistry, the assimilation of CO2 by green plants during photosynthesis leads to the formation of phosphoglyceric and phosphopyruvic acids, and that malic acid is a subsequent product of the reaction. One can speculate that the fundamental processes of CO2 assimilation known for plants can also be assigned for people.

There is evidence sufficient to believe that coenzyme A, which is the physiologically active form of pantothenic acid in animals, is in limited supply in Myasthenia Gravis. This special enzyme is chemically situated at the gateway to the Tricarboxylic Acid Cycle where it "intercepts" pyruvic acid at the end point of glycolysis. The absence or reduced supply of this coenzyme is actually due to the absence or reduced supply of cocarboxylase. When it is present, it not only splits the carboxyl group (COOH) away from pyruvic acid to form CO2 and "free" H, with the "H" being positively ionized, but it also bonds or joins the remaining two carbon fragments of pyruvic acid, known as active acetate, to form acetyl coenzyme A. This leaves the low-energy package niacin-adenosine-dinucleotide (NAD) free to pick up two molecules of hydrogen. (At one time it was thought that the low-energy package was diphosphopyridine nucleotide (DPN), but through the employment of radioactive isotopes and the electron microscope, this was proved to be in error.) One molecule from the carboxyl group of pyruvic acid, and the second molecule from the sulfur group of coenzyme A, makes a high-energy package with the "call letters" NADH2. One method in getting coenzyme A from pyruvic acid, which has been established for heart tissue by Koroes et al., is the reaction between pyruvic acid, coenzyme A, and diphosphopyridine nucleotide (DPN or coenzyme I), in the presence of diphosphothiamine, which is cocarboxylase. There are other important low-energy packages operative in this system and necessary for good health. Flavin-adenosine-dinucleotide (FAD) picks up two molecules of hydrogen to form the high-energy package FADH2 and adenosine diphosphate (ADP). Adenosine diphosphate picks up available PO4 radicals to form adenosine-5-triphosphate (ATP).

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