Page 1, 2,
3, 4, 5, 6, 7,
Next
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 polio viruses, 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, Stern1 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. Moore3, 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."
We also offer the entire Klenner
Protocol for MS article as a 174KB .pdf.
To read it
requires the free Adobe Reader (formerly Acrobat Reader).
Don't have it? Download it from Adobe's
site.
|
