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Thiamine

Thiamine

Description

Thiamine (also spelled thiamin or designated as B 1) is a vitamin, which simply means 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, although it was recognized as early as 1897, there was a naturally occurring "anti-beriberi substance" in rice polishings, 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.
 

Method of Action

Biochemistry
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 cell 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 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. 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 release of energy which accomplishes work.

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.

Thiamine pyrophosphate is a cofactor in at least 24 different enzymes, but its most important role is in 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.

New research
Much evidence has accrued in recent years that dietary indiscretion plays an enormous role in the modern world. Because it is widely believed diet in America is among the best in the world, nutritional disease has been rejected by most physicians as being impossible. Even an obvious presentation of beriberi has been reported as "a metabolic myopathy" of unknown cause. This philosophy blinds the clinician who is taught to think almost exclusively of infectious organisms as the cause of most diseases. A disease of brain is called encephalitis, heart muscle a myocarditis, and nerves, neuritis. The postfix "itis" means "inflammation of", implying the disease process is the result of infection.

Unfortunately the nutritional deprivation conditions seen today are increasingly known as "marginal". The main expression is behavioral and appears to be "psychologic" in nature. Hence, parents, school and associates may be blamed, rather than nutrition. There seems little doubt that wide acceptance of high concentrations of sugar and various stimulants is having a devastating effect on many American children and most physicians do not accept the premise, simply because it is against their training and learned dogma.

A blood test known as transketolase is capable of revealing a state of thiamine deficiency with precision, and clinical experience finds the test is frequently positive. It is a common observation to see a patient's violent mood swings, anxiety and hostile behavior respond to ingestion of two or three hundred milligrams of thiamine a day given as a dietary supplement, under proper medical supervision. This is particularly notable when such an individual has received psychotherapy, sometimes for years, that proved unbeneficial.

It is well known that alcoholics frequently become thiamine deficient and large doses of the vitamin can be very beneficial to such individuals. 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 vitamin as 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. If the diet is assessed for its vitamin content it may be passed as adequate and the idea of vitamin deficiency might be discarded.

An example can be cited. A six year old child had repeated episodes of a condition known as ataxia. Any stress event such as an infection, or head injury, even an inoculation, would trigger an episode of loss of balance and disorientation similar to that seen sometimes after an excess of alcohol.

A "preventive" dose of 600 mg of thiamine a day is required all the time but in the face of any form of stress, such an infection, he doubles or even triples that dose. 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 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 I and II. 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 a normal pharmaceutical dose of a drug may cause symptoms of toxicity.
 

Properties & Uses

Thiamine has been recorded as being effective in more than 230 diseases. This gave rise to so much skepticism that thiamine was rejected as a therapy on the basis that a "cure-all" could not exist.

Of particular interest is the disulfide derivative of thiamine which is found in the allium species of plants, which includes the garlic plant. Known as allithiamine, it is biologically much more active than thiamine hydrochloride.

The most modern synthetic allithiamine is thiamine tetrahydrofurfuryl disulfide (TTFD) which has great promise for therapeutic application. Therapeutic doses of thiamine and TTFD must be much larger that the usual physiologic dose.
 

Consequence of Deficiency

It is relatively easy to understand 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 the classic thiamine deficiency disease in man is beriberi, a disease which affects the nervous system and heart most. However, beriberi is not due to pure thiamine deprivation; it is seen commonly in people whose diet is predominately white rice and is still occurring in poorly nourished populations.

Therefore it is most probable 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 energy metabolism.

Experimental thiamine deficiency has been induced in human subjects, a very risky procedure. The interesting thing about this experiment is the effect on the experimental subjects was that they developed symptoms which are conventionally considered to 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 a very 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 us.

The point to be 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, it does, but rarely in its fully developed state as described in medical textbooks of yesteryear. An example of this was reported. A number of youngsters who were ingesting a 'typical American diet' were found to be thiamine deficient. Symptoms were those described typically as psychologic and most had received psychotherapy without benefit.

Restoring healthy biochemical nervous system function with thiamine and a few other vitamins given as food supplements reversed the symptoms and an abnormal blood test which revealed the deficiency became normal. It was considered the main culprit in these patients was an abundance of high calorie foods and drinks which have unfortunately become a way of life in America.
 

Toxicity Factors

The safety of the vitamin is very great and thousands of milligrams must be ingested in order to produce a toxic effect. Because of the structure of the molecule, the toxic action is similar to the drug known as hexamethonium which is used for 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, a principle which is becoming extremely important in the pharmaceutical use of vitamin and mineral supplements.

Thiamine, like other vitamins, is best taken as a supplement with meals. Although other vitamins relate closely to thiamine in their various individual reactions, little is known about the necessary total vitamin balance that is optimally required. However, it is well understood magnesium plays a very important and fundamental role as cofactor in some enzymes for which thiamine is also cofactor. Indeed, the symptoms of thiamine deficiency are an almost complete facsimile of those caused by magnesium deficiency.
 

Recommended Dietary Allowance

 

age RDA (mg) RNI (mg)
 
infants/children    
0-6 months 0.3 0.2
6-9 months 0.4 0.2
10-12 months 0.4 0.3
1-3 years 0.7 0.5
4-6 years 0.9 0.7
7-10 years 1.0 0.7
 
males    
11-14 years 1.3 0.9
15-18 years 1.5 1.1
19-50 years 1.5 1.0
51+ years 1.2 0.9
 
females    
11-14 years 1.1 0.7
15-50 years 1.1 0.8
51+ years 1.0 0.8
 
pregnancy 1.5 0.9
lactation 1.6 1.0



The average physiologic requirement of thiamine is about 0.5 mg per 1000 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 large amounts can be lost in urine.

For over thirty years, Recommended Daily Amounts has existed in the United Kingdom. It has been used to measure the adequacy of an individual's diet. However, in 1991 the Committee on Medical Aspects of Food Policy (COMA) gave forth a whole new set of figures upon the request of the Department of Health's Chief Medical Officer. Reference Nutrient Intake (RNI) is one of these sets collectively known as "Dietary Reference Values." RNI is an amount of a nutrient that is enough for almost every individuals, even someone who has high needs for the nutrient. This level of intake is, therefore, considerably higher than what most people would need. If individuals are consuming the RNI of a nutrient they are most unlikely to be deficient in that nutrient.

Food Sources

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 gm. whereas whole rice contains 0.5 mg per 100 gm. and rice bran 2.3 mg per 100 gm., illustrating the dietary importance of the part of the plant which is so frequently discarded. The vitamin is also found in wholemeal wheat flour and is almost nonexistent in white flour.

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 thiamine, but the addition of high concentrations of sugar increase the need for the vitamin.
 

Abstracts

References

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