154 Introduction to Human Nutrition
of the foot, then the muscles of the calf, and fi nally
the extensors and fl exors of the thigh. At this stage
there is pronounced toe and foot drop: the patient is
unable to keep either the toe or the whole foot
extended off the ground. When the arms are affected
there is a similar inability to keep the hand extended:
wrist drop.
The affected muscles become tender, numb, and
hyperesthetic. The hyperesthesia extends in the form
of a band around the limb, the so-called stocking and
glove distribution, and is followed by anesthesia.
There is deep muscle pain, and in the terminal stages,
when the patient is bed-ridden, even slight pressure,
as from bedclothes, causes considerable pain.
Wet beriberi
The heart may also be affected in beriberi, with dilata-
tion of arterioles, rapid blood fl ow, and increased
pulse rate leading to right-sided heart failure and
edema, so-called wet beriberi. The signs of chronic
heart failure may be seen without peripheral neuritis.
The arteriolar dilatation probably results from high
circulating concentrations of lactate and pyruvate
as a result of impaired activity of pyruvate
dehydrogenase.
Acute pernicious (fulminating) beriberi:
shoshin beriberi
Heart failure without increased cardiac output, and
no peripheral edema, may also occur acutely, associ-
ated with severe lactic acidosis. This was a common
presentation of defi ciency in Japan, where it was
called shoshin (meaning acute) beriberi; in the 1920s
some 26 000 deaths a year were recorded.
With improved knowledge of the cause and
improved nutritional status, the disease has become
more or less unknown, although in the 1980s it
reappeared among Japanese adolescents consuming a
diet based largely on such high-carbohydrate, low-
nutrient, foods as sweet carbonated drinks, “instant”
noodles, and polished rice. It also occurs among
alcoholics, when the lactic acidosis may be life-
threatening, without clear signs of heart failure. Acute
beriberi has also been reported when previously
starved subjects are given intravenous glucose.
Wernicke–Korsakoff syndrome
Whereas peripheral neuritis, acute cardiac beriberi
and lactic acidosis occur in thiamin defi ciency associ-
ated with alcohol misuse, the more usual presentation
is as the Wernicke–Korsakoff syndrome, due to central
nervous system lesions.
Initially, there is a confused state, Korsakoff ’s psy-
chosis, which is characterized by confabulation and
loss of recent memory, although memory for past
events may be unimpaired. Later, clear neurological
signs develop: Wernicke’s encephalopathy. This is
characterized by nystagmus and extraocular palsy.
Post-mortem examination shows characteristic brain
lesions.
Like shoshin beriberi, Wernicke’s encephalopathy
can develop acutely, without the more gradual
development of Korsakoff ’s psychosis, among
previously starved patients given intravenous glu-
cose and seriously ill patients given parenteral
hyperalimentation.Thiamin requirements
Because thiamin has a central role in energy-yielding,
and especially carbohydrate, metabolism, require-
ments depend mainly on carbohydrate intake, and
have been related to “non-fat calories.” In practice,
requirements and reference intakes are calculated on
the basis of total energy intake, assuming that the
average diet provides 40% of energy from fat. For
diets that are lower in fat, and hence higher in carbo-
hydrate, thiamin requirements may be somewhat
higher.
From depletion/repletion studies, an intake of at
least 0.2 mg of thiamin/1000 kcal is required to
prevent the development of defi ciency signs and
maintain normal urinary excretion, but an intake of
0.23 mg/1000 kcal is required for a normal transketo-
lase activation coeffi cient (see below).
Reference intakes are calculated on the basis of
100 μg/MJ (0.5 mg/1000 kcal) for adults consuming
more than 2000 kcal/day, with a minimum require-
ment for people with a low energy intake of 0.8–
1.0 mg/day to allow for metabolism of endogenous
substrates.Assessment of thiamin status
The impairment of pyruvate dehydrogenase in
thiamin defi ciency results in a considerable increase
in the plasma concentrations of lactate and pyruvate.
This has been exploited as a means of assessing
thiamin status, by measuring changes in the plasma
concentrations of lactate and pyruvate after an oral