Thiamine (also spelled thiamin) is a vitamin, which
simply means that it is vital to life. Like all vitamins, it must be ingested
as part of the diet of all living organisms. Some microscopic one cell
organisms and plants are able to synthesize it. It is noteworthy that, although
it was recognized as early as 1897 that there was a naturally occurring
"anti-beriberi substance" in rice polishing, its chemical structure was not
determined until 3 decades later and it was synthesized in 1938. The
fundamental role of the vitamin in its various forms is to enable oxygen to be
used in the process known as oxidative metabolism, whereby energy is produced
for cellular function.
Thiamine pyrophosphate is a cofactor in at least 24
different enzymes, but its most important role is as an enzyme which enables
glucose to be used as a fuel. Thiamine triphosphate has its most important role
in brain and nerve tissue and this is quite different from the other roles that
the vitamin plays. It appears to have a vital part in energizing nerve tissue
in order that normal messages can be transmitted through the entire nervous
system. Since the nervous system is the most metabolically active tissue in the
body, this high energy compound has a crucial place in governing the high
consumption of oxygen which is the hallmark of metabolic rate.
METHOD OF ACTION
This vital substance stands astride the mechanism by
which glucose is used as fuel to deliver energy for cellular function. It can
be compared to a spark plug in an internal combustion engine, but energy
metabolism in mammalian cells has an incredible complexity and our knowledge of
this has increased greatly in recent years. Thiamine illustrates this
complexity, for one of the most important molecules in the cells is phosphate.
When phosphate is added to a biologic substance it provides it with a means of
storing energy. The main storage of energy in cells is in the form of adenosine
triphosphate, which means that it possesses a high energy potential in
electrochemical terms. A lower energy potential would exist in adenosine
diphosphate and lower again in monophosphate. Thiamine works in a similar
manner. It is "energized" by adding one, then two and finally three phosphate
molecules. In each of these different forms the vitamin has a separate and
different action in cell chemistry. It must be understood that energy can only
be stored by using energy. Put simply, work has to be done (energy utilization)
in order to pull back a bow string. The energy is stored in the form of the
taut string and the arrow is shot from the bow at the will of the archer, by
releasing the bow string. The bow string can be compared to both adenosine and
thiamine in its lower or higher energy state. When energy is required for cell
function, a phosphate is yielded and the adenosine or thiamine drops down to a
lower energy potential. This transfer results in the release of energy which
Unphosphorylated thiamine is called "free thiamine" and
appears to have no biologic activity at all. When it is in the form of
monophosphate its function is poorly understood. It is best known in its
diphosphate or pyrophosphate form, for it is used to energize a large number of
enzyme systems in the body. An enzyme is a protein which acts as a catalyst in
synthesizing a new molecule by a chemical reaction with another molecule, and
this action requires energy. Part of this energy is derived from a vitamin or
mineral which is known as a cofactor to the enzyme.
A blood test known as transketolase is capable of
revealing a state of thiamine deficiency with precision, and clinical
experience finds that the test is frequently positive.
It is well known that alcoholics frequently become
thiamine deficient. There are several reported conditions in which thiamine
dependency exists. A vitamin dependency is a condition where an enzyme requires
a much greater concentration of the vitamin as a cofactor than is usually
required. Thus the normal RDA is totally insufficient, and the patient will
develop symptoms which are identical to those seen in nutritional deprivation.
The message provided by Mother Nature is quite clear. We
must continually adapt to the stresses of environment that beset us. If we fail
to do so we become sick. If the failure is complete, we die. Vitamins and
minerals are the catalysts in the union of oxygen with food (fuel) to provide
the energy to drive the adaptive response. This explains the fact that we are
unable to live without any one of these three essential components. Thiamine is
one of the vitamin team, no less and no more essential than the others.
ANTAGONISTS OF THIAMINE
Tea contains a substance antagonistic to thiamine, and
there are several molecules which block its action, such as pyrithiamine and
oxythiamine. The most important naturally occurring substances which destroy
the molecule are a pair of enzymes known as thiaminases 1 and 11. Both are
produced by a number of bacteria which are found in human bowel and also are
found in some shellfish and the intestines of other ocean fish. All these
substances have been largely ignored as a potential for human disease.
Thiamine, like other vitamins, can enhance the
effectiveness of drugs, so that normal pharmaceutical dose of a drug may cause
symptoms of toxicity.
CONSEQUENCE OF DEFICIENCY
It is relatively easy to understand that the most
metabolically active organs suffer when there is a deficiency of this vitamin,
since there is a high rate of oxygen consumption where there is a fast
metabolic rate. Therefore it is not surprising to find that the classic
thiamine deficiency disease in man is beriberi, a disease which affects the
heart and nervous system most. However, beriberi is not due to pure thiamine
deprivation; it is seen commonly in people whose diet is predominantly white
rice and is still occurring in poorly nourished populations. Therefore it is
most probably that there is a variable degree of vitamin deficiency in general.
The key factor is the high calorie, exclusively carbohydrate diet, and thiamine
is closely linked to metabolism of this dietary component. But other vitamins
and minerals are required in addition because these substances are members of a
nutritional team and must work together in order to use oxygen efficiently in
Experimental thiamine deficiency has been induced in
human subjects, a very risky procedure. The interesting thing about this
experiment is that the effect on the experimental subjects was that they
developed symptoms which are conventionally considered to by psychologic and
psychosomatic. They became irritable, quarrelsome, difficult to live with, and
complained of headaches, abdominal pain, nausea, diarrhea, constipation and
many other symptoms indicating an unbalanced, irritated nervous system. It is
unusual today for a physician or a psychologist to consider the possibility of
faulty nutrition as a cause of psychologic illness. But psychoanalysis or
tranquilizers cannot correct such symptoms if they have a biochemical origin.
In this connection it is of extreme importance to
emphasize that any form of physical or mental stress will exacerbate symptoms.
Hence it is easy to become misled in interpreting the cause of such symptoms.
Obviously, if the metabolic engine is abnormal, it will cause abnormal effects
in the nervous system which then expresses itself in abnormal behavior. It is
not the stress that produces the effect merely because it is stress, any more
than a steep hill can be blamed for causing an internal combustion engine to
falter in an automobile that is climbing it. Either there is something
basically wrong with the engine, or it is being provided with the wrong fuel to
meet engine specifications.
This factor was responsible for a mistake that was made
for a long time in beriberi. Among the Chinese factory workers there was
widespread nutritional deficiency which could be relatively silent as far as
symptoms. In the early part of the summer when they felt the first heat of the
sun, beriberi would suddenly emerge as heart failure or nerve paralysis in many
people at the same time. It was natural to think of an infectious epidemic as
the cause and many physicians in those days thought this way. It was just as
difficult for the early discoverers of vitamins to persuade their medical
colleagues that diseases like beriberi, pellagra and scurvy were caused by
malnutrition as it is today to emphasize that nutritional disease is still with
The point is made again, because it cannot be overstated,
is that oxidation of calorie-providing food must be matched to the presence of
sufficient vitamin and mineral spectrum. If the calorie load is
disproportionate it is very much like choking an internal combustion engine.
The mixture is too rich! Stressing the "engine" under these circumstances calls
upon increased utilization of stored energy. The inability to provide it
represents "the last straw to break the camel's back" and the disease emerges
as the evidence.
A major question here is whether classic deficiency
disease of this type exists in developed countries, and in America in
particular. The answer, unfortunately, is that it does, but rarely in its fully
developed state as described in medical textbooks of yesteryear.
Because of the structure of the molecule, the toxic
action is similar to the drug known as hexamethonium which is used for the
treatment of high blood pressure. It acts by causing an inhibitory action on
certain nerve terminals. Oddly enough, the symptoms of thiamine deficiency are
similar to those produced by an excessive amount ingested.
RECOMMENDED DIETARY ALLOWANCES
The average physiologic requirement of thiamine is about
0.5 mg per 1,000 calories ingested, giving the equivalent of 1.5 mg per day. An
active man might require 2.0 mg per day. However, the body is incapable of
storing the vitamin in its free form and it can become biologically inactivated
under stress so that large amounts can be lost in the urine. A diet with an
excess of refined carbohydrates increases the demand considerably, as does a
high stress level.
Adult Males - 1.5 mg
Adult Females - 1.1 mg
Children 7 to 10 years - 1.0 mg
Infants - 0.4 mg
Pregnant and Lactating Women - 1.6 mg
Thiamine is present in high concentration in yeast and in
the pericarp and germ of cereals. It is present in practically all plant and
animal tissues. Polished rice contains only 0.03 mg per 100 g, whereas whole
rice contains 0.5 mg per 100 g and rice bran 2.3 mg per 100 g, illustrating the
dietary importance of the part of the plant which is frequently discarded. The
vitamin is also found in whole meal wheat flour and is almost nonexistent in
It is a water soluble, white crystalline solid which is
oxidized by potassium ferrocyanide in the presence of alkali to a blue pigment
called thiochrome. This is a basis for detecting the presence of the vitamin in
urine. It is surprisingly stable, even when heated as in cooking, if it is in
the crystallized state or in an acid solution. It is less stable in alkaline
solution and is destroyed by ultraviolet light. Widely used products, including
bread and cereals, are now enriched with synthetic thiamine, but the addition
of high concentrations of sugar increase the need for the vitamin.