Thiamin

BACKGROUND

Thiamin is a water-soluble substance that occurs in free or phosphorylated forms in most plant and animal tissue. It plays an essential role in the supply of energy to the tissue, in carbohydrate metabolism and in the metabolic links between carbohydrate, protein and fat metabolism. Following ingestion, absorption of thiamin occurs mainly in the jejunum, actively at low concentrations and passively at high concentrations. It is transported in blood in both plasma and red blood cells. If intake is high, only a small amount of the thiamin is absorbed and elevated serum values result in active urinary excretion (Davis et al 1984). The total body content of the vitamin is about 30 mg.

Although there is a lack of direct evidence, it is thought that a relationship exists between thiamin requirement, energy supply and energy expenditure. This arises from the role of thiamin as thiamin pyrophosphate in the metabolism of carbohydrate. Thus a small adjustment (about 10%) to estimated requirements is often made to reflect differing body size and energy requirements between genders and in physiological states such as pregnancy and lactation.

Thiamin is found predominantly in cereal foods. There is mandatory thiamin enrichment of baking flour in Australia but not in New Zealand. There is little information about the bioavailability of thiamin. It has been shown that absorption does not differ from supplements given with breakfast or on an empty stomach (Levy & Hewitt 1971).

Low levels of thiamin intake may be associated with biochemical and possibly clinical evidence of thiamin depletion. The early stages of deficiency, however, may be overlooked (Lonsdale & Shamberger 1980) as signs are non-specific. The two distinct major diseases from deficiency of thiamin are beri beri and Wernicke-Korsakoff syndrome. They do not usually occur together.

Beri beri is now rare in countries where it was originally described – Japan, Indonesia and Malaysia – in those living on polished rice. In Western countries, occasional cases are seen in alcoholics. In acute beri beri there is a high output cardiac failure, warm extremities, bounding pulse, oedema and cardiac enlargement. These features appear to be the result of intense vasodilation from the accumulation of pyruvate and lactate in blood and tissues. There are few ECG abnormalities. Response to thiamin treatment is prompt, with diuresis and usually a full recovery. Chronic beri beri affects the peripheral nerves rather than the cardiovascular system. There is inability to lift the foot up (foot drop), loss of sensation in the feet and absent ankle reflexes.

Wernicke's encephalopathy is usually seen in people who have been drinking alcohol heavily and eating very little. Alcohol requires thiamin for its metabolism and alcoholic beverages do not contain it. Occasional cases are seen in people on a prolonged fast (such as hunger strikers) or with persistent vomiting (as in severe vomiting of pregnancy). Clinically, there is a state of quiet confusion, a lowered level of consciousness and ataxia. The characteristic feature is paralysis of one or more of the external movements of the eyes (ophthalmoplegia). This, and the lowered consciousness, respond to injection of thiamin within two days, but if treatment is delayed the memory may never recover. This memory disorder, with inability to retain new memories and sometimes confabulation, is called Korsakoff's psychosis after the Russian psychiatrist who first described it. Wernicke-Korsakoff syndrome (WKS) was apparently more common in Australia than other countries that fortified bread with thiamin. Since mandatory fortification of Australian bread with thiamin in 1991, WKS has become very uncommon (Truswell 2000).

It is not clear why one deficient person develops beri beri and another develops WKS or why the two deficiency diseases seldom occur together. Possibly acute beri beri occurs in people who use their muscles for heavy work and so accumulate large amounts of pyruvate, producing vasodilation and increased cardiac work, while encephalopathy is the first manifestation in inactive people.

There are several indicators for estimating requirements of thiamin (Brin 1970, Schrijver 1991, Wood et al 1980) including low urinary excretion; low erythrocyte transketolase activity; low erythrocyte thiamin or elevated thiamin pyrophosphate effect. Urinary thiamin is the most widely used indicator, but erythrocyte transketolase activity is regarded as the best functional test of thiamin status (McCormick & Greene 1994). However, erythrocyte transketolase activity has some limitations when setting an EAR, as it can be affected by factors other than diet. Erythrocyte thiamin is more stable in frozen erythrocytes, easier to standardise and less susceptible to other factors influencing enzyme activity (Baines & Davies 1988).