B vitamins

Thiamine (Vitamin B1): Wernicke-Korsakoff and Beriberi

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Vitamin B1 (thiamine) and its derivatives serve many roles in the body. It functions primarily as a co-factor to help enzymes perform their molecular reactions. Several important biochemical reactions in which thiamine plays a crucial role include:

(1) Conversion of pyruvate to acetyl-CoA.
(2) Conversion of α-ketoglutarate to succinyl-CoA.
(3) Conversion of glyceraldehyde-3-phosphate to ribose-5-phosphate.
(4) It is used by the enzyme branched-chain α-keto acid dehydrogenase.

All of these reactions are crucial to human biochemistry. The conversion of pyruvate to acetyl-CoA feeds important molecules into the Krebs cycle, which allows the cell to produce energy.

The conversion of α-ketoglutarate to succinyl-CoA is necessary for the Krebs cycle to continue “spinning”. Without vitamin B1 (thiamine) the cycle would slow resulting in decreased energy production.

Thiamine is also important in the production of NADPH via the pentose phosphate pathway. NADPH plays a crucial role in biochemistry because it donates its electron pairs to numerous anabolic reactions.

The breakdown of branched chain amino acids such as valine, isoleucine, and leucine are also dependent on thiamine. The product that results from the breakdown of these amino acids are α-keto acids. They can also be fed into the Krebs cycle to replete molecules in the pathway that may have been siphoned off for other purposes. Maple syrup urine disease is a disorder of branched chain amino acid catabolism.

Since thiamine is involved in many energy producing pathways it is found abundantly in tissues that produce and use lots of energy. These include, but are certainly not limited to, the brain, muscle, and liver.

Role in Disease

Thiamine is a water soluble vitamin that is not actively stored in the body. It therefore must be obtained in the diet. Deficiencies can cause numerous disorders.

One such disorder is Wernicke-Korsakoff’s syndrome. It is seen in chronic alcoholics who may not be obtaining adequate nutrition. In Wernicke’s encephalopathy patients present with nystagmus (ie: jerky eye movements), ophthalmoplegia (ie: inability to move the eyes), and ataxia (ie: a wobbly unsteadiness).

These patients are often very confused. If Wernicke’s encephalopathy is left untreated it can progress to Wernicke-Korsakoff’s syndrome, in which the patient also develops short term memory problems and confabulations (ie: making up stories that aren’t true).

Another disease of thiamine deficiency is known as beriberi. There are numerous forms of this disease. It can affect infants who are being breast fed by thiamine deficient mothers, or who are receiving formulas with inadequate thiamine. In its worst case, infantile beriberi can manifest as severe heart problems.

Beriberi can also affect adults. The adult form exists in two types: wet and dry. Dry beriberi refers to the development of symmetric neuropathies (ie: damage to the peripheral nerves). Both sensory and motor nerves can be involved, and it tends to affect the parts of the nerve furthest from the spinal cord (ie: near the hands and feet). Wet beriberi is the combination of neuropathy plus heart problems, which can range in severity from cardiomegaly (ie: an enlarged heart) to congestive heart failure.

There is no evidence that excess thiamine (vitamin B1) causes any significant health problems. It is well excreted by the kidneys.

Diagnosis

Deficiencies of vitamin B1 (thiamine) are diagnosed by adding the vitamin to a preparation of the patient’s red blood cells. An increase in the activity of the transketolase enzyme is diagnostic of deficient levels.

Treatment

Treatment of thiamine deficiency is, you guessed it, giving the patient thiamine. If the patient has significant disease such as Wernicke’s encephalopathy thiamine can be given IV. Otherwise, oral supplementation and/or "prescribing" a diet rich in thiamine can be used to replenish any deficiencies.

Overview

Vitamin B1, also known as thiamine, is a vital component of numerous cellular reactions, especially those involving carbohydrate and amino acid catabolism (ie: breakdown). When deficiencies exist, several different diseases can occur. They include, but are not limited to, Wernicke-Korsakoff’s syndrome and beriberi. There are no known problems with excessive levels of thiamine since excess vitamin is efficiently excreted in the urine. Diagnosis of deficiencies are made by adding the vitamin to a preparation of the patient’s red blood cells. An increase in the activity of transketolase, an enzyme that relies on thiamine as a co-factor, is considered diagnostic of deficiency.

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