Vitamin B1 deficiency

11.7.1 Causes and effects
A defi ciency of vitamin B1 may occur in situations of
poor diet, chronic alcoholism, excessive diarrhoea or
vomiting, malabsorption and genetic metabolic defects.
Overloading the tissues with glucose without
adequate thiamin coverage can precipitate defi ciency,
as can the use of diuretics. Diseases in which the metabolic
rate is elevated (e.g. hyperthyroidism) can also
lead to defi ciency. Some researchers have demonstrated
that secondary defi ciency of a particular B-group
vitamin can be induced by excessive dosing with
another vitamin of this group. On the other hand,
defi ciencies in vitamins B6 and B12 induced vitamin
B1 defi ciency in rats, even when dietary thiamin levels
were normal (Nishino & Itokawa, 1977). Howard et al.
(1974) confi rmed that folate defi ciency in rats impairs
thiamin absorption.
In humans, a lack of vitamin B1 has widespread
effects, causing anorexia and associated weight loss,
gastrointestinal disturbances, peripheral and central
neuropathy, muscle weakness, and cardiovascular
irregularities. With severe vitamin B1 deprivation,
mental changes develop such as loss of emotional
control, paranoid trends, manic or depressive episodes
and confusion. The classic disease resulting
from a gross defi ciency of vitamin B1 in humans is
Thiamin (vitamin B1) 283
beriberi, which is prevalent in Far Eastern populations
where polished rice is the staple diet. Not only is this
diet defi cient in vitamin B1, but the high carbohydrate
intake increases the requirement for the vitamin, and
the consumption of antithiamin factors will exacerbate
the defi ciency. In other parts of the world where
such a diet is not consumed, chronic alcoholism gives
rise to the Wernicke–Korsakoff syndrome, a form of
beriberi that affects the brain. Subclinical vitamin B1
defi ciencies are characterized by mental disturbances,
fatigue, and loss of weight resulting from anorexia and
digestive problems.
Note: The term ‘polyneuritis’ applies to the involvement
of the peripheral nervous system only, while the
symptoms of central nervous system dysfunction are
more appropriately called ‘encephalopathy’ (Dreyfus,
1976).
11.7.2 Metabolic consequences of vitamin
B1 defi ciency
Proper functioning of the nervous and cardiovascular
systems relies upon normal carbohydrate metabolism,
and this in turn depends upon a dietary supply
of vitamin B1 for conversion to TPP. The pyruvate
dehydrogenase complex and α-ketoglutarate dehydrogenase,
which require TPP as a coenzyme, are
important in the main energy-yielding pathway of
carbohydrate metabolism, the tricarboxylic acid cycle.
The activities of these enzymes are decreased in selective
regions of the brain that are reversibly damaged
as a result of vitamin B1 deprivation (Butterworth et
al., 1985, 1986). The decreased enzyme activities are
due not only to a decrease in the level of coenzyme,
but also of apoenzyme. It is logical to suppose that
impairment of these dehydrogenases due to vitamin
B1 defi ciency will lead to loss of energy production
in the form of ATP. Actually, this does not happen
– at least not in the brain. The brain fi nds alternative
metabolic pathways to bypass the TPP-dependent
steps, thereby maintaining and even increasing energy
production. One possible pathway is the GABA shunt,
which bypasses α-ketoglutarate dehydrogenase (Page
et al., 1989) (Fig. 11.7). Thus energy deprivation is not
believed to be the direct cause of brain lesions resulting
from vitamin B1 defi ciency, although the compensatory
metabolic changes necessary for maintaining
energy may affect biosynthetic processes.
Preventing the synthesis of acetylcholine through
lack of conversion of pyruvate to acetyl-CoA will
impair nerve impulse transmission at synapses, and
blocking the pentose phosphate pathway through
impaired transketolase activity will lead to a reduced
synthesis of DNA through lack of ribose. Dreyfus &
Hauser (1965) showed that transketolase is more
severely affected by vitamin B1 deficiency than is
pyruvate dehydrogenase, and the reduction of transketolase
activity is anatomically correlated to brain
lesions.