thiaminetxt

4 - Thiamine (vitamin B1) deficiency
Thiamine (vitamin B1) deficiency was discovered early
in the twentieth century as the cause of beriberi, an
illness that developed mainly in countries where whole-
grain rice had been replaced by refined white rice as
the dietary staple [1, 2]. Causes ranging from
infection, toxic contamination of water, dietary
deficiency of nitrogen (protein) among others, to racial
predispositions were sought, but adding back to rice
"polishings" containing the germ removed during
refining was found to immediately ameliorate the
symptoms of this illness. One difficulty in the discovery
of causation was to actually extract the infinitesimal
amount of the anti-beriberi factor in the whole grain.
Diligent research finally led to isolation of thiamine as
the essential molecular component that would prevent
illness [3]. Subsequently thiamine was synthesized [4],
which led to a cost-efficient way of enriching not only
refined rice but other grains as well.

Thiamine is an essential cofactor for enzymes that
catalyze glucose metabolism, and it is now therefore
classified as a vitamin (vitamin B1). Thiamine is
needed only in small amounts, but it interacts with
enzyme proteins to catalyze the chain of biochemical
reactions required for aerobic metabolism thus has a
high turnover rate and needs to be replaced at least
daily [5]. Calingasan et al (1994) measured
distribution of the major thiamine-dependent enzyme,
alpha-ketoglutarate dehydrogenase, and found the
highest amounts in regions of the brain that are
predilection sites for Wernicke’s encephalopathy [6].

Neurological signs gave evidence of brain involvement
in beriberi. Peripheral "polyneuritis," disorders of eye
movements, staggering gait, disorientation, and
drowsiness were noted to be similar to the problems of
chronic alcoholics, and thiamine deficiency was found
to produce the same bilaterally symmetric lesions of
brainstem nuclei characteristic of Wernicke's
encephalopathy [7]. The neurological impairment
caused by alcohol abuse may in part be secondary to
deficiency of thiamine and other vitamins, not only
because alcohol addiction includes neglect of good
nutrition but chronic alcohol use can also damage the
gastrointestinal tract and interfere with absorption of
thiamine. Detoxification and long-term treatment of
alcoholism therefore includes giving thiamine.

The terminal stage of beriberi includes opisthotonos, a
severe rigidity of the limbs and backward arching of the
spine. Opisthotonos is often referred to as
"decerebrate rigidity" and it can be produced in
experimental animals by a cut between the superior
and inferior colliculi. The inter-collicular cut is thought
of as a bidirectional disconnection of forebrain from
hindbrain influences. Compromise of aerobic
metabolism therefore brings about a similar
disconnection whether through asphyxia or deficiency
of the essential cofactor thiamine. Figure 2 (chapter 8)
is from the article by Miller and Myers (1970) and
shows opisthotonos (or decerebrate rigidity) in a
monkey two days after resuscitation from 24 minutes of
circulatory arrest [8]. Opisthotonos has also been
described in case reports of people who have suffered
severe head injury with trauma to the midbrain tectum;
see for example the paper by Denny-Brown (1962) who
proposed that the tectum is susceptible to traumatic
damage when impacted by the tentorium sheath that
separates the cerebellum from the midbrain [9}.

Because thiamine is an essential cofactor for enzymes
of the aerobic metabolic pathway; its deficiency can be
viewed as a form of cellular asphyxia, or suffocation at
the molecular level. It should come as no surprise then
that patterns of brain damage similar to Wernicke's
encephalopathy occur in cases of cardiac arrest,
ischemia, asphyxia or suffocation. Figure 14 shows
damage of the inferior colliculus that occurred in a
patient maintained on total parenteral feeding to which
thiamine had not been added [10].

Carpenter KJ (2000) Beriberi, White Rice, and Vitamin B: A Disease, a
Cause, and a Cure. Berkeley: University of California Press.
Williams RR (1961) Toward the Conquest of Beriberi. Cambridge, MA:
Harvard University Press.
Peters RA (1936) The biochemical lesion in vitamin B1 deficiency. Lancet,
May 23, 1161-1165.
Cline JK, Williams RR, Finkelstein J. (1937) Synthesis of vitamin B1. Journal
of the American Chemical Society 59:1052-4. Reprinted (1977) in
Nutrition Reviews 35:238-40.
Schellenberger A (1998) Sixty years of thiamin diphosphate biochemistry.
Biochimica et Biophysica Acta 1385:177-186.
Calingasan NY, Baker H, Sheu KF, Gibson GE (1994) Distribution of the
alpha-ketoglutarate dehydrogenase complex in rat brain. Journal Of
Comparative Neurology 346:461-479.
Dreyfus PM, Victor M (1961) Effects of thiamine deficiency on the central
nervous system. American Journal of Clinical Nutrition 9: 414-425.
Miller JR, Myers RE (1970) Neurological effects of systemic circulatory
arrest in the monkey. Neurology 20:715-724.
Denny-Brown D (1962) The midbrain and motor integration. Proceedings
of the Royal Society of Medicine 55:527-538.
Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient
encephalopathy following prolonged parenteral nutrition. Journal of
Neurology, Neurosurgery and Psychiatry 55:826-829.