| Warning: Don't apply this without your doctor's consultation. For your doctor's information, some further ingredients suggested in Dr. Klenner's 1984 writings (such as IV niacin), made available with a warning NEVER to try this on your own, as there are several ingredients that could cause serious reactions, and must be tested on you by a doctor or alternative practitioner.
How
to read Dr klenner's protocol EASILY!
You
will notice that some parts of the protocol are a bit diffucult
to comprehend due to medical terms (if ofcourse you're not a doctor).
I believe though that you can learn many things the same way I did.
I have tried to make the protocol easier to read through your computer
or by printing it. As you can see I have created contents for easy
access to certain parts and stressed on certain characteristic words
or meanings in order to focuse while reading it.
Also
keep in mind that this protocol has been written in 1973. This means
there still may be things to be included in the therapy of MS...
maybe your doctor will help! One thing is for sure. It is the best
way to treat your MS permanently.
If
you want to have it as originally published in 1973, in PDF format,
download it here
Frederich
Klenner defines an orthomolecular treatment of MS
that has been effectively employed by Dale Humpherys and other patients.
(For Humpherys’ report, see his article in the December 2005
issue of the Townsend Letter for Doctors & Patients.)
Keywords: Klenner, protocol, MS, multiple, sclerosis,nerve, pathology,
vitamin b, metabolites, orthomolecular, peripheral
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
Journal of Applied Nutrition, 1973
The protocol of how to effectively treat Multiple
Sclerosis. (In two parts, as originally published
in 1973.)
Part I:
Two devastating pathological syndromes affecting nerves
are Multiple Sclerosis and Myasthenia
Gravis. To adequately understand the significance of these
diseases, one must have a working knowledge of fatigue,
normal and abnormal. The phenomena of fatigue
according to Starling’s Principles of Human Physiology has
been recognized for years to depend on two factors:
1) the consumption of the substances available for the supply of
potential energy to the contractile material;
2)
The accumulation of products of the contractile process. We must
consider a third: The inability to use available energy-producing
substances because of distribution roadblocks.
Two
general locations for normal fatigue
are:
1)
At the synapses, the delicate junction between neuron and neuron,
recognized as highly susceptible to fatigue;
2)
The junction between motor nerves
and the fibers of skeletal muscle, made possible by motor end plates.
Synaptic fatigue and end plate fatigue
occur in such minute structures that quick recovery seems always
possible. We must recognize, however, that although the feeling
of fatigue may apparently be quickly
dissipated, actual restoration of the fatigued
structure will require much time.
When a plant is fatigued it wilts;
unless relieved of the fatigue, it
dies. Proper atmospheric conditions, proper soil, or these equivalents
conferred by man will restore, to some degree, the faltering plant.
Even prayer has been advanced as an active agent to not only relieve
the failing plant of its fatigue, but
also to encourage its growth. Plants do indeed have a soul –
the soul of growth. This predicates a potential capable of responding
to “kindness” of various types. In this light, then, people
with “green thumbs” are nothing more than accepted plant
missionaries. When an animal is fatigued,
it usually follows an innate faculty supplied by nature and rests.
When sick, like the dog, it will eat grass to relieve the gastric
complaint. The dog’s master can go further and supply various
drugs or vaccines to either cure the malady or to prevent several
types of illnesses from ever coming into existence. Animals have
not only a soul for growth like the plant, but also a soul of sensation.
Proper rest, proper drugs and proper food, along with understanding,
will secure for the dog mental and physical relaxation, thus assuring
the animal a more serene and longer life as compared to a dog running
loose on the streets or in the wild, and required by circumstances
to scavenge for itself.
It is a common experience to obtain marked relief from physiological
fatigue by taking a short nap, the
often-called“Edison cat nap.” An ordinary night’s
rest is none too long for recovery from fatigue
created by a day’s labor. The almost universal habit of abstaining
from ordinary duties one day out of seven has real significance
It acknowledges the necessity of allowing, at intervals, a longer
period for restoration than the usual nightly ones in order that
accumulative fatigue will not be experienced.
Work is labor, and so is play. There is a real and significant difference
between being pleasantly tired and being fatigued. The share-cropper
working in the field, where fresh air abounds, can easily expend
far more energy than one who works in a poorly-ventilated factory,
yet the farm worker will register only relative fatigue,
as compared to the factory worker who often will be physiologically
exhausted. This suggests that oxygen plays an important role in
the production of fatigue.
Muscle
Fatigue
In the laboratory one can demonstrate that repeated stimulation
of striated muscle diminishes the force of the contraction, and
that indefinite repetition of such stimulation will so exhaust the
muscle that eventually it will fail to respond. The fatigue
which is here observed can be due either to the exhaustion of the
glycogen and the hexose phosphates or to the accumulation of lactic
acid within the muscle. Muscle contraction is essentially an anaerobic
process. Lactic acid production, the fundamental chemical reaction
producing energy for muscle contraction, does not require oxygen.
Such energy-yielding reactions of partial decomposition, not requiring
oxygen, are called fermentations. Muscle, then, obtains energy independently
of its immediate oxygen supply by the rapid fermentation of glycogen
to lactic acid, in the same way as brewer’s yeast derives energy
by the fermentation of sugars to alcohol. This anaerobic explosion
of energy is akin to jet propulsion, and similarly, its potential
is limited. Ultimately, muscle requires oxygen for the maintenance
of normal irritability, for oxidative energy production, and for
the restoration of its anaerobic energy-yielding system. Muscle
action and muscle fatigue is indeed
a very complex chemical system. Such units as phosphocreatine, adenosine
triphosphate and calcium and magnesium ions deserve limited explanation.
Eagleston and others, independently, discovered that most of the
creatine in muscle is in labile combination with phosphoric acid.
The free creatine which occurs in muscle fatigue
is proportional to the amount of phosphocreatine which is decomposed.
Creatine is derived in the body from the amino acids Arginine and
Glycine, plus a labile methyl group.
According
to Cameron and Gilmour, creatine, in acid solution, readily loses
water to give a ring compound, an internal anhydride, creatinine.
Creatinine is a constant constituent of urine, and its amount is
sometimes increased in the later stages of nephritis and always
in Myasthenia Gravis. The simplest
conception of creatine-creatinine metabolism is that creatinine
is formed from creatine during periods of muscular activity when
creatine is transiently free in muscle, and then passes by way of
the blood, without change, into the urine. Creatine phosphate breaks
down in the presence of adenosine diphosphate (ADP) to form adenosine
triphosphate (ATP). Creatine phosphate acts as the immediate energy
source for the synthesis of adenosine triphosphate for relatively
short periods during bursts of contractile activity. The usable
life of creatine phosphate is limited. Once it is used up by muscle
action, the muscle must then rely on the adenosine triphosphate
(ATP) which is synthesized during the chemical activity of the Kreb
cycle in glycolysis. Adenosine triphosphate is the essential high-energy
package, and it is responsible for delivery of necessary power for
the activation of all cells; it is the basic energy unit for life.
During muscle relaxation phase, some of the adenosine triphosphate
reacts with creatine to form creatine phosphate at the expense of
adenosine triphosphate which is reduced to adenosine diphosphate
(ADP), a low-energy package. This change of reactions continues
until such a situation exists when muscle cells can no longer synthesize
ATP due to lack of oxygen and essential substrates.
When
this happens, a state of muscle rigor mortis exists. Frequently,
Myasthenia Gravis patients experience
minimal rigor mortis; sometimes no adenosine triphosphate is available
and so actual death. We must briefly discuss still other phases
of muscle activity. The filaments in skeletal muscle are composed
primarily of the proteins actin and myosin. Small amounts of other
proteins play important roles in the contractile cycle. Part of
the energy for movement comes from the splitting of adenosine triphosphate
by the myosin molecule. Actin increases the ability of myosin to
split adenosine triphosphate. Magnesium ions and calcium ions are
also necessary in muscle action. Besides actin, tropomyosin and
troponin are responsible for the effects of calcium on the contractile
apparatus. One must also consider the part played by acetylcholine
and its esterase in muscle activity. Too much or too little of these
substances prevents or slows down muscle action even when all other
factors are within normal limits. The neuromuscular junction potential
can be modified by drugs and disease. One such drug is curare. Curare
merely occupies a reactive site so that acetylcholine is prevented
from interaction with motor end plates. Myasthenia
Gravis is a disease whereby too much pyruvic acid (pyruvates),
due to faulty metabolism, affects the interaction of acetylcholine
at the site of the motor end plates at the neuro-muscular junction.
In
Multiple Sclerosis, the sluggish and
sometimes bizarre muscle activity is due to absence or inability
to utilize essential factors because of mechanical and chemical
roadblocks. Like nerve action potential,
muscle action potential is an all-or-none event. The overall effects
of motor unit recruitment depend upon the anatomical relationship
between the contracting units. Specifically whether the fibers are
in series or parallel. When linked in parallel by connective tissue,
the force generated by each fiber is additive, producing a total
force proportional to the number of fibers contracting. When the
fibers are in series, the total force is equal to that generated
by a single fiber no matter how many fibers fire simultaneously.
These relationships exert quite a different effect on the degree
and velocity of shortening. No matter how many fibers in parallel
contract together, the amount of shortening and velocity are the
same as when a single fiber contracts, but both the degree and the
velocity of shortening are proportional to the number of contracting
fibers in series. Long muscles shorten more and faster than short
muscles; thick muscles exert more tension than thin muscles.
These
differences, however, disappear when the values are expressed per
unit length and
cross-section
area. The total range of length changes a muscle can undergo while
attached to the bone is much less than the changes that would cause
the active tension to fall to zero. Muscle exerts a force on the
bones to which they are attached through tendons. As muscle shortens,
it exerts only a pulling force called flexion. Opposing muscles
straighten the unit flexed which is known as extension. This review
on muscle action and fatigue is,apologetically,
very elementary, but sufficient to establish a basic understanding
of what is happening in the pathological conditions entertained
in this treatise.
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
carboxyhemoglobin.
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 enzymemediated 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. Biochemists 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).
Protein
and Lipid Metabolism
In dealing with muscle and nerve pathology,
the metabolism of lipids and protein must also be considered, although
in a lesser degree. There is a close relationship between neutral
fats and glucose metabolism. The neutral fats, consisting of three
fatty acids attached to the three-carbon molecule glycerol, constitutes
the majority of the lipid in the body. The breakdown and synthesis
of neutral fats is closely associated with the metabolism of glucose
because of the formation of intermediates common to both pathways.
The breakdown of fatty acids requires coenzyme A and hydrogen carriers
such as niacin-adenosine-dinucleotide (NAD).
Ascorbic
acid can operate as a hydrogen transport in cellular oxidation,
thus facilitating these reactions. The starting point for fatty
acid synthesis is acetyl coenzyme A. In the diseases in which we
are concerned, myelin is very important.
myelin is a fat-like substance forming
the principle component of the myelin
sheath of nerve fibers. It is composed
of cholesterol, certain cerebrosides, phospholipins and fatty acids.
Protein metabolism is far more complicated than lipid or carbohydrate
metabolism. Proteins are formed from 20 different amino acids, all
of which have different chemical structures and require different
pathways for their synthesis and degradation. Synthesis of a protein
molecule from amino acids involves more than the formation of chemical
bonds between amino acids. The amino acids must be placed in a precise
sequential order. Unlike fats and sugars, amino acids contain nitrogen
in addition to carbon, hydrogen and oxygen. It is more than of academic
interest to know that thiamin hydrochloride is a pyrimidine compound,
thus containing nitrogen, like amino acids. Because of this amine
factor, Funk originally spelled vitamin
with an “e” – vitamine.
“Vit” comes from the Greek “vita,” meaning life,
and E amine for the nitrogen factor. Since only thiamin hydrochloride
of all vitamins had this factor, the “e” was dropped,
and the name vitamin retained for symbolic
reasons. Although all amino acids are important, some more than
others, and still others necesary for the continuance of life, the
one we are interested in is the amino acid glycine. Glycine is noted
for its specific dynamic action. Bodansky states that not only does
the body use any preformed glycine that may be present either in
the diet or in the tissues, but it is forced, at times, to synthesize
this amino acid in large amounts. The conversion of glycine into
sugar in the animal body has been well documented.
Rapport and Katz have shown that when glycine is added to perfused
muscle, the oxygen absorption is 40% higher than otherwise, indicating
that the presence of the amino acid glycine stimulates the combustion
of other tissue constituents. Glycine with the amidine group from
arginine, through a process of trans-amidination and transmethylation,
yields creatine.
Comparison
Between Multiple Sclerosis and Myasthenia
Gravis
Myasthenia Gravis and Multiple
Sclerosis differ only in that the former will not require
as intensive treatment as will Multiple Sclerosis.
The answer for this difference is obvious. One is a peripheral nerve
pathology, the other being central
nerve pathology.
In
the diagnosis, one will find the eyelids in Myasthenia
Gravis drooping. In Multiple Sclerosis
there will be nystagmus – constant involuntary, more or less
cyclical movement of the eyeballs. Movement may be in any direction,
but usually lateral as the patient follows the examiner’s finger.
(It is definitely more pronounced than that found in Meniere’s
disease.)
There
may be heaviness of the legs in Myasthenia
Gravis, but it will always be present in at least one leg
in Multiple Sclerosis.
Myasthenia
Gravis patients will have difficulty in chewing and swallowing,
the jaws might sag, and some will present a sad, masked-like expression,
but never like Parkinson’s disease. Scanning speech will be
in evidence in advanced cases in Multiple
Sclerosis, and words will
come slow and syllabic.
General
weakness increases as the day goes on in Myasthenia
Gravis; some increase in fatigue
only with activity in Multiple Sclerosis.
Remissions
and exacerbations are common in both diseases in the early stages,
but more so with Myasthenia Gravis.
In
Multiple Sclerosis, the patients will
experience numbness of the hands and legs as the disease progresses,
or a tremor in the hand will develop, making signing of one’s
name a
problem. The tremor is intentional. Well along in the disease of
Multiple Sclerosis, the gait will be
awkward and stiff.
Ataxia
is due mainly to the inability to coordinate and control movements.
The knee-jerks will be exaggerated, with positive Babinski and ankle
clonus. The Babinski can be normal and no clonus, but there are
other signs equally as important. Oppenheim’s tibia test; Gordon’s
calf muscle test; Chaddock’s external malleolus test, and the
Hoffman reflex – a finger reflex. Any one of these, along with
temporal whiteness of the optic nerve
can be considered early or minimal Multiple
Sclerosis. Abdominal reflexes are variable. Pain, bi-lateral,
of the sartorius muscles with any positive reflex is always very
suspicious of Multiple Sclerosis.
In Myasthenia Gravis, the old neostigmine
test is conclusive. More detailed symptoms and signs on these two
pathological conditions can be found in such common reference as
Merck’s Manual. The important factor is early diagnosis. Do
not hesitate to commence treatment in either disease even though
the impression might be guarded. Response to treatment is sufficient
evidence that your judgment is sound.
There
are three forms of Multiple Sclerosis:
1)
Pseudo-Multiple Sclerosis or Cerebral,
which is the syndrome characterized by mental symptoms, emotional
lability, convulsive seizures, hemiplegia and aphasia. This type
is caused by an Adenovirus which gains entry into the brain through
damage to the choroid plexus much like the encephalitis that follows
pneumonias. Actually, the resulting pathology
is an encephalitis. Many who have
experienced this syndrome have died; many who have lived might just
as well have died, for the return trip is costly, long, and requires
a great amount of tender, loving care.
2)
Cerebellar-brain-stem-spinal: this is true Multiple
Sclerosis and is manifested by nystagmus, scanning speech,
intention tremor, ataxia, transient paresthesias, weakness
in one or more extremity, and visual disturbances.
3) Spinal or minimal Multiple Sclerosis:
These cases are never given a diagnosis. These patients come with
other complaints, but singular upper motor neuron pathology
will be evident. This might be, as we have seen them, positive Hoffman,
positive Gordon, positive Oppenheim, and occasionally, a patient
with a footdrop limb.
Importance of Thiamin Hydrochloride
in Neurological Diseases
The importance of thiamin in treating Myasthenia
Gravis and Multiple Sclerosis
cannot be over-emphasized. Two molecules of thiamin hydrochloride
in combination with two molecules of phosphoric acid is cocarboxylase.
For the reaction to acetyl coenzyme A plus oxaloacetic acid to continue
through to citric acid with the release of coenzyme A, cocarboxylase
must be present. If this reaction does not take place, due to one
of many factors, there will be no coenzyme A present to react with
another molecule of pyruvic acid to set in motion the elements necessary
for the continuance of the metabolic cycle. In thiamin deficiency,
both pyruvates and lactate accumulate in the blood.
Pyruvates also accumulate at the neuro-muscular junction causing
cloudy swelling of the distal portion of the nerves.
Cocarboxylase, also known as diphosphothiamine, is necessary in
the synthesis of acetyl-choline and in the control of its hydrolysis.
The activity of choline esterase of serum is also strongly inhibited
by cocarboxylase.
The chief chemical factor in both diseases is thiamin hydro-chloride.
Other fractions of the B-complex are also essential but in lesser
amounts.
Myasthenia
Gravis is due to genetic fault, most likely involving an
intermediate lethal gene or group of genes.
Multiple
Sclerosis is more complex. The initial pathology
is sickness caused by the Coxsackie virus. This virus mimics poliomyelitis,
and for many years accounted for thousands of so-called polio cases.
This virus, like the polioviruses, can cause paralysis but never
permanently. The nerve damage is the
result of microscopic hemorrhages in the central nervous system.
With the contraction of the scar at the site of bleeding, the vessels
carrying nutrients to the nerve cells
are virtually clamped off. This leaves nerve
tissue, in many instances, alive but not capable of work.
As
time goes on, this wasting of nerve
tissue results in loss of its myelin
protection. This is similar to electrical wires that have lost their
insulation when exposed to the wear of daily use, or exposure to
the elements.
Myelin
is a lamellated structure composed of neurilemma cell membranes.
Neurilemma cells have marked affinity for axis cylinders, apply
themselves closely and seemingly engulf them. At the same time their
cytoplasm flows around the axis cylinder. The myelin
sheath is actually part of the neurilemma plasma membrane with its
lipid and protein layers. myelin in
the central nervous system is likewise lamellated. It is laid down
by neuroglia cells. The sheath of the nerve
fiber is known to have a relationship to speed of conduction –
the speed of propagation being in direct proportion to the fiber
diameter. Impulses are thought to travel along the surface of a
nerve fiber and its speed over the
large myelinated fibers is approximately 337 miles per hour, 150
meters per second.
We
can reconstruct the nerve pathways
and re-myelinate the damaged nerve
channels. There is nothing new about this physiology. Each one of
us has demonstrated or experienced positive Babinski reflexes. A
child is born without completed laminated sheath.
This is the reason for the spastic movements of the child. The nerve
channels are minute in comparison to the adult person, thus we can
expect a longer interval of time necessary for repair. If the baby
can complete the myelination of its nerve
channels with only mother’s milk, surely we can duplicate this
performance – and we can. There will, however, be situations
where the pathology has existed for
so long a time that recovery seems impossible. This is true because
it requires approximately two years of treatment, with massive doses
of vitamins and a high protein diet, to repair one year of the disease.
Physicians
are too afraid to make an early diagnosis, and some patients now
under my care experienced as much as ten years in that process.
In Myasthenia Gravis, the chief concern
is with the build-up of pyruvic acid at the neuro-muscular junction.
We also find decreased amounts of acetyl-choline along with limited
amounts of cocarboxylase. As we noted in the discussion of glycolysis,
cocarboxylase plays a very important role in various reactions involving
principally the decarboxylation of pyruvic acid and other keto acids.
In the brain, cocarboxylase participates in the anaerobic dismutation
of pyruvate to lactate and acetate, and their subsequent oxidation
to carbon dioxide and water.Cocarboxylase is also involved in the
synthesis of acetylcholine which is definitely in short supply in
Myasthenia Gravis. The activity of
choline esterase is strongly inhibited by this same double thiamin
unit.
The
conversion of thiamin hydrochloride to cocarboxylase takes place
in the liver, the kidneys and to a small degree, in brain and muscle.
One can have nephritis, yet the small amount manufactured in the
kidneys continues to be produced. The liver is the main source for
this conversion. An individual with liver pathology
would have a decreased capacity for phosphorylation of thiamin.
The storage capacity of the body for thiamin is limited. It does
accumulate rapidly in the liver in its original form and also as
the pyrophosphoric ester. Thiamin deficiency inhibits lactic acid
metabolism at the stage of pyruvic acid. When we refer to thiamin
deficiency, we actually mean a lack of cocarboxylase. Pyruvic acidemia
is an index of this type of thiamin deficiency. We might mention
here that niacin deficiency can induce hepatic insufficiency. The
amount of nicotinic acid required to elevate blood coenzyme, the
active physiological form of nicotinic acid, increases dramatically
in liver stress. Cocarboxylase (thiamin pyro-phosphate) operates
as a coenzyme in the oxidative decarboxylation of ketoglutarate
to succinate and of pyrovate to acetoacetate. Succinic acid in turn
is acted upon by the enzyme succinic dehydrogenase, yielding fumaric
acid by oxidative dehydrogenation. Fumaric acid readily undergoes
hydration in the presence of the enzyme fumarase to form malic acid,
which on oxidation in the presence of the enzyme malic dehydrogenase,
yields oxalacetic acid. At this point of cell metabolism, the entrance
of another molecule of pyruvic acid follows the Krebs cycle to be
repeated. We are never concerned with the amount of pyruvic acid
formed by the various routes, provided we can maintain normal cell
metabolism.
Early
Use of Thiamin Hydrochloride in Neurological Diseases
In the late thirties, Stern(1) from Columbia University, was employing
thiamin hydrochloride intraspinally with astonishing results in
Multiple Sclerosis. He reported taking
patients to the operating room on a stretcher, and following 30
mg. thiamin given intraspinally, they would walk back to their room.
The response was relatively transient, but it led Stern to believe
that Multiple Sclerosis was nothing
more than vitamin B1
avitaminosis, the “modus operandi” being damage to the
filter bed of the choroid plexus. Stern also found that the effective
dose of vitamin B1,
when given in the lumbar subarachnoid space, was too close to the
lethal dose as was demonstrated in dogs. Stern’s hypothesis
was backed by the knowledge that degeneration of the myelin
sheaths of peripheral nerves as well
as of the ganglion cells of the brain and spinal cord can be produced
in experimental polyneuritis.
Similar
findings are observed in starvation, even when the supply of thiamin
appears to be adequate. One school of thought regards the neurological
syndrome of polyneuritis as a functional defect concerned with the
neurons. From 30 years of observation, I am certain that in Myasthenia
Gravis and Multiple Sclerosis,
it is not a functional defect, nor is it due to impaired diffusion
which would deny to the total metabolism sufficient quantities of
the vitamin to satisfy the requirements
of the neuro-muscular systems. The problem is supply and demand.
In
this light, Dr. Leon Rosenberg2 of Yale University Medical School,
in working with B vitamins, distinguishes between vitamin-deficiency
diseases and vitamin-dependent diseases. He states that the successful
treatment of vitamin-dependent diseases
requires dosages up to 1,000 times the calculated minimal daily
requirement. 1.3 mg. has been established for thiamin hydrochloride
which would indicate that in the pathological conditions being considered,
the daily requirement would be at least 1300 mg.
Moore
3, in 1940, published a monograph on the use of high intravenous
doses of nicotinic acid for the cure of Multiple
Sclerosis. Moore employed a drug combination called “Nicobee.”
This preparation contained 100 mg. nicotinic acid and 60 mg. of
thiamin in each 10cc solution.
Many of the components of the B-complex must also be administered
in varying amounts, along with thiamin hydrochloride, since they
too exert a dynamic influence in general metabolism. Many believe
that the B vitamins are actually metabolic reagents.
Hoagland
has referred to them as “protective catalysts.”
Part
II: Recommended Treatment Schedule
1) Thiamin hydrochloride: 300mg to 500mg, 30 minutes before meals
and bed hour, and during the night if awake. The higher amounts
in long-standing cases. This requirement is high, since much is
lost through action of gastric juices and loss due to perspiration;
400 mg. daily by needle, given intramuscularly. During summer months
this can be given every 12 hours to good advantage. Two to three
times each week, and where office access is convenient, 20 mg. per
kg. body weight, or at least 1000 mg. is administered intravenously.
This is given with 100 mg to 200 mg. Niacin (nicotinic acid) which
is available 100 mg. in 10cc ampules. (The concentrated Niacin,
available in 30cc vials, must be diluted if employed intravenously.)
The intravenous dose is given with the patient in a recumbent position.
A 20cc to 30cc syringe, carrying a one-inch 22-gauge needle should
be employed. The injection is given slowly (5 to 7 minutes) holding
the syringe with one hand. The usually-employed three fingers of
the other hand must be on the patient’s pulse. An increased
pulse rate indicates too fast a flow of the medicine. This indicates
the rate of phosphorylization. Thiamin hydrochloride is, indeed,
a toxic substance, and anaphylactic reactions have been reported,
but I have never seen a case in treating thousands of patients,
(not necessarily Myasthenia Gravis
or Multiple Sclerosis), in 30 years
of clinical observation. I have observed one case of extreme sensitivity
in which itching was present within one minute after an intramuscular
injection of 100mg. This was immediately controlled with 5cc Benadryl,
IM.
It
must be remembered that once thiamin hydrochloride is phosphorylated,
it is no longer a critical allergic substance, but is cocarboxylase,
a necessary but absolutely harmless agent. (My problem has been
the preservatives now required by FDA regulations, and they should
be removed.) Higher doses of thiamin can be used, but then the dilution
factor must be greater.
2) Niacin (nicotinic acid): We
recommend 100mg to 3 grams, thirty minutes before meals and at bed
hour, and also during the night if awake – whichever dose will
produce a strong body flush. Niacin dilates the blood vessels, even
those that have been compressed by scar tissue, allowing a greater
amount of nutrient material to reach the cell laboratory or factor
comprising muscles and nerves. This
constant, repeated dilatation of the blood vessels acts in the same
manner as the dilating urethral catheter to correct constriction.
One is chemical, the other is mechanical. Hot fluids taken at the
same time as the niacin will enhance the flush. Pyridoxine has been
a suggested stimulant. The lack of constant flushing in Multiple
Sclerosis is disappointing but not hopeless. It will require
a longer time to achieve results. Many times patients will flush
with intramuscular niacin when they fail to flush by the oral route.
An occasional patient will experience the sensation of a chill following
nicotinic acid flush. This is transient and of no consequence.
Food,
even jelly beans or a glass of milk, will prevent or minimize the
experience. Some patients will flush sometimes and not at other
times, even during a single day. If no flush develops within 45
minutes, the dose should be repeated. A delayed reaction of several
hours can occur, and should this be superimposed upon a previous
medication, the result could be severe. Do not scratch when itching
from niacin. Just press the area with your fingers, or better still,
with a cube of ice. Antihistamines will stop the itching and limit
the flush, should this be necessary.
Niacin should be given very slowly by the intravenous route in the
geriatric patient, with or without cardiac pathology,
since it can produce dilatation great enough to effect right-side
heart failure. Myasthenia Gravis patients
sometimes attain geriatric status. Vasomotor collapse of peripheral
vessels, although rare, can occur. Eight mg. Decadron given IM will
reverse this condition.
3) Pyridoxine (vitamin B6):
Lack of this vitamin has been shown
to induce microcytic hypochromic anemia and neurologic lesions in
dogs and pigs. The term B6 includes
not only pyridoxine, but also pyridoxal and pyridoxamine, all three
compounds being found in nature. These derivatives have biological
activity equal to that of pyridoxine, as demonstrated in rats. Pyridoxine
plays a part in the metabolism of unsaturated fatty acids. It is
also important in the metabolism of amino acids. Pyridoxal phosphate
functions as a coenzyme, and in transamination reactions; 100mg
to 200mg is given before meals and bed hour. At least 100mg daily
is given intramuscularly.
4) Cobalamin (vitamin B12):
It is thought that vitamin B12
acts as a catalyst in the formation of the purine and pyrimidine
deoxyribosides which are present in deoxyribonucleic acid. Technically,
B12 is cyanocobalamin. vitamin
B12 with pterylglutamic reduces the
requirement for choline essential in the treatment of neurological
diseases; 1000mcg. is given three times each week by needle (repository
type). The incident of dermatitis from continued use of vitamin
B12 by needle is roughly 15%. I have
never seen this develop in a patient with Myasthenia
Gravis or Multiple Sclerosis.
B12 is recognized as a factor in the
synthesis of myelin.
5) Ascorbic Acid (vitamin C): The use
of high daily doses of vitamin C will
prevent a superimposed illness and will lend itself in metabolism.
Ten to twenty grams should be taken daily by mouth in divided doses.
6) Riboflavin (vitamin B2):
A deficiency of vitamin B2
in young animals results in inhibition of growth terminated by death.
The yellow enzyme can, as demonstrated by Warburg and Christian,
participate in a series of enzyme reactions involved in the metabolism
of carbohydrates. It is capable of transporting hydrogen from reduced
coenzyme II, a niacin coenzyme which attacks hexosemonophosphate,
regenerating the riboflavin phosphate-protein complex. Riboflavin
also takes part in enzymic reactions as a dinucleotide prosthetic
group, consisting of riboflavin, two phosphoric acids, ribose and
adenine. Riboflavin is very important in the regulatory function
of the hormones involved in carbohydrate metabolism. It is classified
as a low-energy package; 40mg to 80mg given daily by needle IM;
25 mg. before meals and bedtime.
7) vitamin E as d-alpha tocopherol
acetate of d-alpha tocopherol acid succinate. The latter is more
practical since it is a pure form. Complex biochemical changes in
the muscle tissue in chronic vitamin
E deficiency are followed by histalogical lesions characteristic
of muscular dystrophy. Deficiency has also been shown to produce
demyelinization and distortion of the axon pattern in the spinal
cord, giving rise to hypalgesia and progressive paresis. Fatal massive
liver necrosis occurs in animals maintained on diets low in vitamin
E and sulfur-containing amino acids; 800 international units before
meals and bedtime must be adhered to in this treatment.
8) Crude liver: This substance contains factors still unknown but
essential in metabolism. Patients with pernicious anemia often show
neurological involvement, and are tremendously benefited by liver
injections which, of course, contain vitamin
B12. Degenerative changes brought on
by other factors, therefore, can also be benefited by daily injections
of crude liver.
9) Adenosine-5-Monophosphoric acid: One of the purine bases occurring
in muscle is adenine. It, along with other purines, exists in various
forms. Adenosine polyphosphate is of primary interest in this discussion.
The basic structure is adenosine, adenine-9-riboside. This is esterified
with phosphoric acid at the 5-position of the ribofuranose, to form
adenosine-5-phosphoric acid, also known as adenosinemonophosphate
(AMP). Inosinic acid is a commonlyoccurring breakdown product of
AMP, formed by deamination in muscle extract. Myosin displays enzymic
activity similar to adenylic deaminase. By attaching further phosphoric
acid residues in pyrophosphate linkage, adenosinediphosphate (ADP)
and adenosinetriphosphate (ATP) are obtained. ATP, as previously
noted, is the energy package
essential for life. By adding this to our treatment, we enhance
all chemistry dealing with cell metabolism.
10) Choline: Choline is a structural component of fat and nerve
tissue, thus has a strong relationship to the phospholipids and
to its acetyl ester. Acetylcholine plays an important role in the
humoral transmission of parasympathetic and other nerve
impulses to effector organs. It also plays a part in transmethylation.
Choline serves as a methylating agent in the physiological process
– guanidoacetic acid to creatine. We give 700mg to 1400mg after
each meal and at bed hour.
11) Lecithin: Lecithin is the glyceryl ester of a pair of fatty
acids and a substituted phosphoric acid group attached to a choline
radical. “Choline” is one of the products of lecithin,
representing about 15% of the molecule. Lecithin placed in water
and observed under the microscope, will diffuse out, forming long,
curving strands (myelin forms).
The hydrophilic nature of the lecithin molecule plays an important
part in the structure and properties of cell membranes. It is the
lipid used in nerve tissue. We give
1200 mg. Soybean Lecithin after each meal.
12) Magnesium: 100mg. after each meal to supply additional ions
for muscle activity. It is an enzyme activator.
13)
Calcium Gluconate (10 grain tablets): We give two tablets after
each meal and at bed hour to supplement dietary intake for muscle
activity. At times, this is given intravenously, one gram twice
weekly.
14) Calcium pantothenate: The physiologically active form of pantothenic
acid is coenyzme A. Its acetyl derivative (acetyl CoA) is synonymous
with active acetate. Metabolic transformations are very complex
and involve numerous enzymes and coenzymes. Coenzyme A participates
in the acetylation of amines. The pantothenic acid coenzyme plays
a vital role in carbohydrate metabolism and acetyl transfer also
occurs in the metabolism of fatty
acids. We give 200 mg. after each meal and at bed hour.
15) Aminoacetic acid (glycine): Glycine enters into a variety of
metabolic functions. It is directly concerned in the synthesis of
glutathione, the tripeptide which plays an important part in intracellular
oxidation and reduction.
Rapport and Katz have shown that when glycine is added to perfused
muscle, the oxygen absorption is 40% higher than otherwise, indicating
that the presence of this amino acid stimulates the combustion of
other tissue constituents. To the body in general, glycine is no
doubt most important because of its wide adaptability in the detoxicating
process of the body. More than one hundred substances, when fed,
are joined in the body with glycine. In the deamination of glycine,
three products will be formed: ammonia, carbon dioxide and water.
The ammonia from this reaction is then quantitatively converted
to urea. One heaping tablespoon of the powder in a glass of milk
four times each day. Much of the oral medication can be taken with
this drink.
16) Make certain that the hemoglobin is at least 13 grams.
17) High protein diet with two to three eggs for breakfast.
18) One Theragram-M cap. daily for trace minerals.
19) Dantrium has value for relieving intentional tremor and Symmetrel
for relieving stiffness in Multiple Sclerosis.
Dose must be individualized.
20) Zinc gluconate: 10 mg. three times each day has some value in
Myasthenia Gravis. Take several hours
after vitamin B2.
This treatment works so dramatically in Myasthenia
Gravis, that should a given patient’s physician refuse
to administer this schedule, I have this recommendation: One gram
thiamin hydrochloride one hour before meals and at bed hour, and
during the night if awake. Niacin taken at the same time, and in
amounts sufficient to produce a good body flush. Two hundred mg.
calcium pantothenate and 100mg pyridoxine before meals and at bed
hour. Ten grams ascorbic acid, taken in divided doses. Amino acetic
acid: one heaping tablespoon in a glass of milk, four times each
day. Naturally, the full schedule will afford more dramatic response.
For a long time, it has seemed to me that virus bodies might have
the potential to alter their protein coat, and therefore their dimension,
and become another virus for another disease. In our long practice,
we would see, as I am certain many of you have, chickenpox just
before Thanksgiving, mumps by Christmas, red measles in the Spring,
and polio or a virus mimicking polio in the Summer. German measles,
virus colds, and virus pneumonitis just about any time.
Etiology of Multiple
Sclerosis – Historical
As for the etiology of Multiple Sclerosis,
a good history will tell the story. I have one patient who was diagnosed
with Polio in 1950. He experienced total paralysis, but made a complete
recovery. Five years ago, he began to demonstrate the signs and
symptoms of Multiple Sclerosis. He
was given a “strong” course of ACTH with relief of symptoms.
Three months later, this had to be repeated, but the results were
not as good. Some three months later, a third series of injections
of ACTH was worthless. (This has been the pattern with the use of
ACTH, and represents nothing more than whipping a tired horse. In
my book, it borders on malpractice.) His myelin
sheath has just about been destroyed. He has so many areas of “no
insulation” that his movements are like that of a newborn baby.
Had he received our treatment at the onset of his illness, he would
be in good health today without any physical handicap.
This individual never had Poliomyelitis. The virus that brought
him down was the coxsackie virus, and this explains his initial
recovery.
Another
case seen was a 31 year-old female. This young lady was diagnosed
Poliomyelitis when she was 19 years of age. Three years ago, she
began developing signs and symptoms of Multiple
Sclerosis, and that is her present diagnosis. Her neurologist,
who made the diagnosis of Polio, now tells her that there is no
doubt in his mind that what she has now, actually started when she
was 19. He is absolutely correct, because she had a coxsackie virus
infection. In 80% of the cases that have come under my supervision,
an illness compatible with a Summer virus has been entertained.
Unless an illness is associated with paralysis, it is understandable
when a patient or the family have difficulty in establishing a workable
timetable.
Other
Hypotheses on Etiology of Multiple Sclerosis
Dr. Henry Kempe, from the University of Colorado School of Medicine,
as reported by Medical World News, believes that Multiple
Sclerosis is caused by vaccinia virus. He found a correlation
between severity of the clinical disease and antibody titer. He
also observed that only in demyelinating disease were antibodies
to vaccinia virus in the cerebral spinal fluid. This brings to mind
the work of Horsefall and his co-workers at the Rockefeller Institute.
They were able to culture an organism, which they designated Streptococcus
MG, from a large percentage of their patients with primary atypical
pneumonia. This proved later to have no value, and the viral nature
of the disease was recognized.
The sleeping virus theory of Dr. Milton Alter and others, as reported
in Medical Tribune, along with the environmental aspect for Multiple
Sclerosis is another “ripe apple” for public consumption
and public press exaggeration. Most of this theory rests with the
circumstantial evidence that filterable transmissible agents having
slow virus properties are present in other diseases.
Another theory, that of Dr. D.K. Schandl, a Nova University biochemist,
in Fort Lauderdale, Florida, and published in The Charlotte Observer,
relates it to an environmental agent, specifically carbon monoxide,
and the lack of the vitamin pyridoxine
(vitamin B6).
Pyridoxine is concerned with the enzymatic decarboxylation of amino
acids and the incidence of Multiple Sclerosis
is too low in terms of the availability of carbon monoxide.
Still another theory has been advanced by Doris Dahl and Amico Bignami
of Stanford University, Palo Alto, California. They report the discovery
of a substance that “may” prevent the self-renewing of
myelin. Scar tissue is indeed the problem,
but it is the end result of microscopic hemorrhages following virus
invasion.
Concepts
Concerning Myasthenia Gravis
In Myasthenia Gravis, the accepted
reasoning is initiated by Thymomas in 20% of patients over forty,
and hyperplasia of the thymus in others. Antibodies to muscle have
been reported in roughly 33%. Excessive pyruvates at the neuro-muscular
junction has been recognized but not appreciated.
Case
Histories
Multiple Sclerosis: Male, white, was
in a wheelchair at a Veterans’ Hospital for two years. Patient
seen while home on 30-day vacation. Treatment given every day with
marked improvement. Upon returning to Veterans’ Hospital, the
physician in charge recognized the improvement and advised the young
man to return home and continue the treatment. After three years,
he was given a clean bill of health by three neurologists in three
different places and was given a responsible position. This was
in 1950. The individual remains in excellent health, but continues
with modified therapy.
Myasthenia Gravis: Male, white, receiving
treatment from nearby medical centre for one year. He was receiving
guanadine (amount unknown) and 90 mg. prostigmine bromide each day.
He was first seen in a Myasthenia Gravis
crisis. The emergency treatment consisted of two ampules of prostigmine
methylsulfate of a strength of 1:2000, and 5cc of coramine. Within
a period of eight or ten minutes, the patient experienced a generalized
convulsive seizure which lasted some five minutes and required 4
men to hold him on the bed. Prostigmine, by needle, was continued
for three weeks, and then 15mg. tablets every six hours. Thiamin
hydrochloride was given three times each day, intramuscularly, as
well as other fractions of the B complex. In one year’s time,
he had been “weaned off” prostigmine. Although given only
two weeks to live by the physicians at the medical centre the day
prior to our first visit, this individual lived a normal life for
18 years. His death was due to a cerebral accident.
Female,
white, with diagnosis (August 1967), Polyneuritis. Began with pain
and burning of legs associated with jerking. Ran high fever 10 days.
Paralysis started on left side along with weakness of hands, soon
followed with complete paralysis lower extremities. Seen first time
7/5/69. Paralysis and weakness as described. Started on medication
by mouth and intramuscular injections. Several months later, began
intravenous schedule. In approximately 16 months, was able to move
right leg. Upper extremities returned to normal. On 6/10/72, began
to move left foot. Patient now able to walk approximately 50 yards
with knee braces and walker. Does all the cooking for family of
four, as well as sewing clothes for herself and two daughters. (I
can personally vouch for her ability as a cook.) April 1973, she
was able to go without a back brace that was previously necessary
for her to use to even get out of bed. One marvels at her ability
to pedal a stationary bicycle “contraption” made for her
by her husband so that she might exercise her legs. Our diagnosis
in this case is Transverse Myelitis. (200 grams ascorbic acid given
IV, in divided doses, would have saved this patient from paralysis.)
She has also received 300mg ribonucleic acid four times each week.
Female, white, who developed weakness in extremities around June
25, 1961. Sensory examination revealed hypalgesia over medial aspect
of right foot and calf. Motor examination revealed a partial foot
drop on the right, with rather marked weakness and inversion, eversion,
and dorsiflexion of right foot. Reflexes upper extremities 3-4 plus.
Abdominal reflexes absent. Knee jerks were 3-4 plus with patellar
clonus. Right ankle jerk was 4 plus and the left, 3 plus. Bilateral,
sustained, ankle clonus. Babinski’s “brisk.”
Later examined and hospitalized at a nearby medical centre where
Medrol was tried. She was sent home with a diagnosis of Multiple
Sclerosis, superimposed by a viral eningoencephalitis. Blurring
of vision was established as due to a left six-nerve
paralysis. Seen in our office one month later, we concurred with
the impression of Multiple Sclerosis.
Our treatment schedule became operative. It has been a long journey
since June 1961, but the results have been phenomenal. This individual
has been returned to full activities, and as a gesture of gratitude,
comes to my office to serve in the capacity of an office assistant
several days each week. She does, however, still maintain her treatment
schedule. Whether this is necessary or not, I follow the advice
of another patient who has been continuing modified treatment for
22 years: “Why stop when you feel so good?”
Male, white, 28 years. Seen first time 2/26/72. History of numbness
in lower extremities with loss of muscle control from waist down.
This started approximately 2 years before this visit. Difficulty
with bladder control at times. Seen by several neurologists at a
nearby medical centre who failed to make a diagnosis other than
to say he had a Central Nervous System pathology.
Babinski’s, Gordon and Oppenheim signs were all positive, and
ankle jerks were 4 plus. Ankle clonus was bilateral and sustained
on right. He demonstrated a right foot drop. We entertained a diagnosis
of Multiple Sclerosis. Treatment was
not started since he had an appointment to be examined at a nearby
Veterans’ Hospital clinic. We advised him not to accept ACTH
therapy. The following week we did start treatment. After 5 weeks,
we did not see the patient again for three weeks, at which time
he confessed that he thought that he was well and had stopped treatment.
The weakness and other symptoms were again returning. He has been
back to gainful employment for the past 12 months. Incidentally,
he has been a “crack” pistol shooter, and he still can
hold a steady hand on the gun.
Female, white, 57 years. Seen first time 5/19/72. Chief complaint
was fatigue. This started approximately
seven years before coming to our office. The onset of illness was
gradual. Generalized weakness as the day went on, but was always
feeling refreshed in the morning. Drooping of the eyelids became
a problem so that she automatically would tilt her head backward
so that the ptosed eyelids would be partially corrected. fatigue
of the muscles of mastication on chewing became so embarrassing
that for the past several months, she avoided all social events,
even dinner with friends. Swallowing also became a serious problem
forcing her to a bland and sometimes liquid diet. Even a few minutes
talking, while taking the history, would so fatigue
her that she found it necessary to recline on the examining table
so as to regain her strength. She visited many clinics and medical
centers in the United States and Europe, but always was given the
same diagnosis – her review of conditions labeled her as psychosomatic.
To us it was obvious that she suffered from advanced Myasthenia
Gravis. 1000mg. Thiamin Hydrochloride and 300mg. pyridoxine
given by needle had her demonstrating jaw and face movements to
her husband in less than 10 minutes. She remarked that she had not
been able to do that in three years. She was given our schedule
for treatment, but had great difficulty getting her local physician
or any physician to give her the needed injections. In desperation,
she returned to one of the medical centres and confronted them with
the diagnosis, which they did not believe. She, however, demanded
that they employ their test for this disease, which they did. From
the patient’s description, given at a later visit, I surmised
that Tensilon was used. Her response was the greatest ever seen
in that University. She is also receiving RNA 300mg. tablets three
times each week, which we believe have stimulated or furthered her
progress. She no longer hesitates to eat in public, and her stamina
is approaching normal. During a visit to our office in April of
1973, she laughed and joked about her experiences in getting the
diagnosis confirmed so that she could receive the vitamin
injections under supervision. She also favored us with a platter
of delicious cakes that she had baked. Although we could write a
book on cases treated and cured (or established a permanent remission),
time is a prohibiting factor.
Conclusion
The treatment of Multiple Sclerosis
has been empiric since it was first described by Sir Robert Carswell
in 1838. Brickner, in 1936, gave a review on treatment which included
preparations of Antimony and Arsenic, fever induced by various methods
such as diathermy, malaria, typhoid vaccine, and fever brought on
with the use of drugs. Surgical procedures such as cervical sympathectomy
and root section were also employed. Serums, hypnotism and intraspinal
injections of lecithin had their day. Moore administered nicotinic
acid and thiamin following the dissertation by Zimmerman and Burack
on diseases of the nervous system resulting from a deficiency of
the vitamin B-Complex, and the paper
by Spies and others on the use of nicotinic acid in the treatment
of Pellagra associated with mental pathology.
Spies and Aring, in 1938, published a paper on the effects of vitamin
B1 on peripheral neuritis as associated
with Pellagra. Moore also had the benefit of the work of Stern,
who published an article on the intraspinal use of vitamin
B1 for the relief of intractable pain,
and for inflammatory and degenerative diseases of the Central Nervous
System. We learned early in our approach to this disease that small
and infrequent doses of thiamin hydrochloride would not accomplish
our purpose, and we also realized that more than one unit of the
B-Complex would be required, even though the physiological chemistry
relative to this phase of metabolism had not been completely established.
Although Moore used nicotinic acid for vasodilation purposes, we
rationalized that the degenerative process taking place in nerves,
and thus also in muscle, was of a greater magnitude. Inasmuch as
the only sickness remembered by the patient, family or relatives
took place during the summer months, we immediately suspected a
virus to be the offending agent.
This idea gained momentum with the greater incidence of Multiple
Sclerosis following the epidemic of encephalitis lethargia
of 1920 to 1926, and the epidemic of encephalitis B in St. Louis
and Toledo in 1934. However, the incidence of Polio was also up.
Mixed, abortive or unrecognized cases of Poliomyelitis became a
tantalizing factor. After the isolation of the Coxsackie virus with
its mimicking of Polio, and the knowledge that the paralysis with
this type virus infection was never permanent, the real devastating
factor, in time and place, at least to me, became apparent. Flexner
and Lewis were able to demonstrate that in Polio, vascular and lymphatic
lesions constituted the primary causes of the lesions of the nervous
system. Multiple hemorrhagic accidents take place in Multiple
Sclerosis with ensuing scar tissue. As these microscopic
scars contract, they impinge on the vessels carrying nutrients to
the Central Nervous System cells. In muscle, the “devastation”
is brought about through lack of function, there being no “electrical
charge” present to keep muscle active. For this reason, the
Sister Kenney treatment for Polio had merit, since it helps to maintain
muscle and muscle-nerve integrity.
Our employment of nicotinic acid is to effect adequate dilatation
of existing vascular structures, producing over time, chemically,
what the Urologist accomplished with his catheters in a mechanical
fashion. Once these channels are sufficiently operative, the metabolic
factors that we supply will go about revamping the myelin
sheaths. Due to lack of full energy components, cells can temporarily
lose the ability of normal physiological activity. We can restore
the normal function of cells which depends upon their ability to
extract and use the chemical potential energy locked within the
structure of organic molecules. We accomplish this by placing massive
amounts of the essential material at the disposal of cells.
We categorically make this statement: Any victim of Multiple
Sclerosis who will dramatically flush with the use of nicotinic
acid, and who has not yet progressed to the stage of myelin
degeneration, as witnessed by sustained ankle clonus elicited in
the orthodox manner, can be cured with the adequate employment of
Thiamin Hydrochloride and other factors of the vitamin
B Complex in conjunction with essential proteins, lipids, carbohydrates
and injectable crude liver. If sustained ankle clonus is not bilateral,
then it is not a deterrent. We have had patients who did demonstrate
bilateral sustained ankle clonus, and who were in wheelchairs, and
who returned to normal activities after 5 to 8 years of treatment.
These patients, fortunately, had not received ACTH. One patient
was given a single course of Medrol 4 mg. QID. This had little effect
on her pathology, and apparently no
blocking action, on our treatment.
The general use of ACTH in Multiple Sclerosis
will extend the recovery period by a time directly proportional
to the amount of the drug employed. It is hoped that this paper
will bring an end to this senseless practice of medicine, since
ACTH never works the third time.
The theories recognized as playing a part in Myasthenia
Gravis still rest in the main with Thymus enlargement or
tumor, Endocrine dysfunction, Metabolic fault, and the build-up
of pyruvic acid in the vicinity of the motor endplates. In reality,
it is a genetic fault involving a lethal intermediate gene or group
of genes. There is definitely an over-supply of pyruvates, and an
under-supply of acetylcholine. The cue in this drama is cocarboxylase.
Coenzyme A is also in limited supply. Two molecules of thiamin hydrochloride,
and two molecules of phosphoric acid yields cocarboxylase. One way
of obtaining acetyl coenzyme A, a by-product of coenzyme A and pyruvic
acid, is in the reaction between pyruvic acid, coenzyme A and diphosphopyridine
nucleotide in the presence of diphosphothiamine (cocarboxylase).
Cocarboxylase is also involved in the synthesis of acetylcholine
and in the control of its hydrolysis. The activity of choline esterase
of serum is strongly inhibited by this same agent. Thiamin occupies
a key position in at least the terminal stages of carbohydrate metabolism.
Cocarboxylase plays an active role in the decarboxylation of pyruvic
and other keto acids. In the brain, cocarboxylase participates in
the anaerobic dismutation of pyruvates to lactate and acetate, and
their subsequent oxidation to carbon dioxide and water. In liver
and other tissue cells, cocarboxylase is involved in the conversion
of pyruvates to oxalacetate which combines oxidatively and irreversibly
with another molecule of pyruvate to enter the tricarboxylic acid
cycle. In thiamin deficiency, a form of peripheral neuritis markedly
demonstrated in some cases of chronic alcoholism exists, affecting
both sensory and motor nerves.
The treatment of Myasthenia Gravis
is that of any pathology dealing with
the interruption of the normal physiology of nerve
cells. In years past, when we were treating Poliomyelitis successfully
with massive doses of ascorbic acid, we would always follow with
an indefinite timetable, giving the B vitamins
for nerve repair. We see the same results
when treating damage to the spinal cord, whether this is due to
mechanical trauma, or to the inflammation caused by a virus –
any virus. As pointed out by Lipschitz et al., the replenishing
of vitamin B1
restores the ability of the nervous system to handle properly pyruvic
acid and dextrose. This action of thiamin makes its function in
Myasthenia Gravis seem elementary.
A German scientist once speculated that cocarboxylase was actually
the “food” required for nerve
life. In treating Myasthenia Gravis
with the schedule outlined, the intensity with which it is applied
in Multiple Sclerosis will never be
necessary. We are not confronted with the loss of myelin
sheaths in extra vital areas. The chemistry, however, is more complex
than in Multiple Sclerosis, since it
involves muscle cells to a greater degree.
Enzymes and their balance is a necessary approach. When we realize
that over 900 different enzymes have been identified, it makes more
knowledgeable the need for extensive vitamin
therapy. This suggests that normal liver function is necessary for
good results. A simple liver function test can be used to good advantage.
One that I worked out many years ago to demonstrate “liver
stress” is performed as follows. Have patient bring 90cc from
first voiding upon arising. Fill ordinary test tube to within one
cm. of top. Allow to set for 24 hours and read. One will find, in
most specimens, a gelatinous fluid resting at the bottom of the
test tube. The amount present, which can measure 2-1/2 cm., indicates
the degree of liver stress present. Choline by needle or by mouth
will remove this finding from the urine. Some urine specimens will
show a heavy, white sediment obstructing proper reading of liver
stress. Glacial Acetic Acid alone, and/or heat will temporarily
remove these phosphates. Should the deposit of phosphate be exceedingly
heavy, then it is advisable to secure a bedtime specimen, or one
2 hours after breakfast. The night specimen should be placed in
a cool area until delivery. Occasionally, the urine specimen will
look like skim milk.
This
is due to earthy phosphates and can be cleared by adding Glacial
Acetic Acid to the tube. (After ascertaining liver stress, one can
then add 20 drops Glacial Acetic Acid to the specimen – if
none was previously added – and allow to remain an additional
48 hours to check for Uric Acid Crystals. A red shower indicating
an abnormal level for uric acid.) This test must be run every week
when administering ribonucleic acid (RNA).
Appendix
Since presenting this paper, we have observed that improvement in
all categories is enhanced when the intravenous injection contains
800 mg. to 1000 mg. thiamin hydrochloride, 200 mg. pyridoxine, 400
mg. niacinamide, 100 mg. nicotinic acid. The thiamin hydrochloride
solution must be clear. The amount of niacin employed must be calculated
from the “flush factor” of a given patient. The injection
is made with a 20cc or 30cc syringe, using a 23G x 3/4 inch or 22G
x 1 inch needle. Intravenous medication can be given daily; it should
be administered at least twice weekly. Due to sensitivity possibilities,
we always have the patient take the intramuscular injections for
three weeks before starting intravenous therapy.
Bibliography
– Papers
1. Stern, E.L.: The Intraspinal Injection of vitamin
B1 for the Relief of Intractable Pain,
and for Inflammatory and Degenerative Diseases of the Central Nervous
System. Am. J. Surg. 34:495, 1938.
2. Rosenberg, L.E.: Vitamin Deficiency
Diseases and the vitamin Dependent
Diseases with Reference to B and D. Natl. Health Fed’n. Bulletin
Vol. XVIII, No. 10, November 1972.
3. Moore, M.T.: Treatment of Multiple Sclerosis
with Nicotinic Acid and vitamin B1.
Archives Int. Med. Vol. 65, pp.18, Jan. 1940.
4. Bijou, S.W.; Baer, I.M.: Child Development II Universal Stage
of Infancy. Appleton-Century-Crofts, 1965.
5. Kempe, C.H.: Key to the Secret of MS.
Medical World News, July 7, 1972.
6. Alter, M. et al.: Dissertation on Environmental and Sleeping
Virus Theory. Medical Tribune.
7. Schandl, D.K.: Dissertation on Environmental and Pyridoxine Cause
of MS. The Charlotte Observer, Charlotte,
NC. April 23, 1973.
8. Dahl, Doris; Bignami, Amico: Report of Substance Preventing Renewal
myelin. Reidsville Review, April 23,
1973.
9. Brickner, R.M.: A Critique of Therapy in Multiple
Sclerosis. Bulletin Neur. Inst., New York, Vol. 4:665, April
1936.
10. Zimmerman, H.H.; Burack, F: Lesions of the Nervous System Resulting
from a Deficiency of the vitamin B
Complex. Arch. pathology, Vol. 13:207,
February 1932.
11. Spies, T.D.; Cooper, C.; Blankenhorn, M.A.: The Use of Nicotinic
Acid in the Treatment of Pellagra. JAMA, Vol. 110:622, February,
1936.
12. Spies, T.D.; Aring, C.D.: The Effect of vitamin
B1 on the Peripheral Neuritis of Pellagra.
JAMA, Vol. 110:1081, April 1938.
13. Klenner, F.R.: fatigue-Normal and
Pathological with Special Consideration of Myasthenia
Gravis and Multiple Sclerosis.
Southern Medicine and Surgery, Vol. III, No. 9; September 1949.
14. Flexner, S.; Lewis, P.A.: Experimental Poliomyelitis in Monkeys.
Journal Experimental Medicine, Vol. 12:227, 1910.
Bibliography
– Textbooks
a.
Alpers, B.J.: Clinical Neurology, 2nd Ed., F.A. Davis Co., 1950.
b.
Bodansky, M.: Intro. to Physiological Chemistry, 2nd Ed. John Wiley
& Sons, Inc., 1930.
c.
Cameron, A.T.; Gilmour, C.R.: The Biochemistry of Medicine. William
Wood & Co., 1933.
d.
Evans, A.L.; Hartridge, E.: Starling’s Principles of Human
Physiology 5th Ed., J&A Churchill, London, 1930.
e.
Fieser, L.F.; Fieser, Mary: Organic Chemistry. 3rd Ed., D.C. Heath
and Company, 1956.
f.
Harrow, B.: Casimir Funk: Pioneer in Vitamins & Hormones. Dodd,
Mead & Co., New York, 1955.
g.
Hawk, P.B.; Oser, B.L.; Summerson, W.E.: Practical Physiological
Chemistry. 13th Ed., McGraw-Hill Book Co. Inc., 1954.
h.
Lichtman, S.S.: Diseases of the Liver, Gallbladder and Bile Ducts,
Vol. I, Lea & Febiger, Philadelphia, 1953.
I.
Lowenberg, S.A.: Medical and Physical Diagnosis. 7th Ed. F.A. Davis
Co., 1948.
j.
Martin, H.N.; Martin, E.G.: The Human Body. 11th Ed. Revised. Henry
Holt and Co., 1932.
k.
Srb, A.M.; Owen, R.A.; Edgar, R.S.: General Genetics, 2nd Ed., W.H.
Freeman and Co., 1965.
l.
The Merck Manual, 12th Ed. Merck & Co., Inc., Rahway, NJ 1972.
m.
The Vitamins: A Symposium, 1939, AMA.
n.
Vander, A.J.: Sherman, J.H.; Luciano, D.S.: Human Physiology McGraw-Hill
Inc., 1970.
o.Wells,
H.C.: Chemical pathology, 5th Ed. Revised.
W.B. Saunders Co., 1925.
Frederich
R. Klenner, BS, MS, MD Reidsville,
North Carolina A native of Pennsylvania, Dr. Klenner attended St.
Vincent and St. Francis Colleges, where he received his BS and MS
degrees in Biology. He graduated magna cum laude and was awarded
a teaching fellowship there. He was also awarded the college medal
for scholastic philosophy. There followed another teaching fellowship
in Chemistry at Catholic University, where he pursued studies for
a doctorate in Physiology. Dr. Klenner then migrated to North Carolina
and Duke University to continue his studies. He arrived in time
to use his knowledge in Physiology and Chemistry to free the nervous
system of the frog for a symposium, by immersing the animal in 10%
nitric acid. Taken in tow by Dr. Pearse, chairman of the department,
he was finally persuaded to enter the school of medicine. He completed
his studies at Duke University and received his medical degree in
1936.
Dr. Klenner served three years in post-graduate hospital training
before embarking on a private practice. Although specializing in
diseases of the chest, he continued to do General Practice because
of the opportunities it afforded for observations in medicine. His
patients were as enthusiastic as he in playing “guinea pigs”
to study the action of ascorbic acid. The first massive doses of
ascorbic acid he gave to himself. Each time something new appeared
on the horizon, he took the same amount of ascorbic acid to study
its effects so as to come up with the answers.
Dr. Klenner’s list of honours and professional affiliations
is tremendous. He is listed in various “Who’s Who”
registers, and has published many scientific papers throughout his
career.
Dr.
Klenner is a Fellow: The American College of Chest Physicians; Fellow
& Diplomate: The International College of Applied Nutrition;
Fellow:
The American Association for the Advancement of Science; Fellow:
The American College of Angiology;
Fellow:
The American Academy of Family Practice; Fellow: The Royal Society
of Health (London);
Fellow
(Honorary): The International Academy of Preventive and Orthomolecular
Medicine; Fellow: International College of Angiology; and
Founder-Fellow: American Geriatrics Society.
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