Vitamin b1(thiamine) and beriberi

Department of Pharmacy
Pokhara University
School of Health and Allied Sciences
Atul Adhikari
Second Semester, B. Pharm.
Pokhara University, Dhungepatan, Lekhnath-12,
Kaski , Nepal
Vitamin B1(THIAMINE) AND
BERIBERI

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Contents
• Thiamine
• Thiamine pyrophosphate
• Clinical indications of thiamine
• Debilities of beriberi
- dry beriberi
- wet beriberi
- Wernicke-Karsakoff syndrome
- GI tract disorders
• Treatment
• Conclusion
• References
Pharmaceutical Seminar I 2

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Thiamine
Properties:
It is water soluble vitamin
Also soluble in methanol and glycerol
Insoluble in acetone, ether, chloroform and benzene
Colorless compound
Molecular formula: C12H17N4CS
Source:
 Foods that are rich in Thiamine: whole wheat bread
and unhusked rice, nuts, milk, yeast, pork, beef, liver,
chicken, and legumes, such as peas.

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Daily RequirementPopulation Age Allowance, mg/d
Recommended Dietary Allowances (RDAs)
Boys 9-13 y 0.9
Men >14 y 1.2
Girls 9-13 y 0.9
Women 14-18 y 1.0
Women >19 y 1.1
Pregnant/Lactating Women . . . 1.4
Children 1-3 y 0.5
Children 4-8 y 0.6
Adequate Intakes (AIs)
Infant 0-6 mo 0.2
Infant 7-12 mo 0.3

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Structure of thiamine
Two different groups are attached:
Thiazolium heterocycle
- methyl group
-2 hydroxy group
-substituted methyl group
Pyridine heterocycle
-amino group
-methyl group
Two groups are linked from pyridine heterocycle
by methyl bridge to nitrogen of thiazole group.
Fig: Thiamine

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• Tissue distribution:
• about 20-30 mg of thiamine is stored in skeletal muscle,
heart, liver, brain, kidneys,
• thiamine present in plasma, milk, CSF
• Absorption and transport:
• released by action of phosphatase and pyrophosphatase in
upper small intestine
• At low concentration transport is carrier mediated
• At high concentration by passive diffusion
• Excretion:
• thiamine and its acid metabolits are released principally in
urine.

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Thiamine pyrophosphate(TPP)
 Biologically most active form of vitamin B1(thiamine)
 Formed by transfer of pyrophosphate group from adenosine
triphosphate (ATP) to thiamine
 The small intestine is where phosphorylation of thiamine takes
place.
 Serves as coenzyme in formation or degradation of α-ketols and
oxidative decarboxylation of α-keto acids.

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Clinical indications of thiamine
• Plays key role as coenzyme in
-oxidative decarboxylation of pyruvate and α-
ketoglutarate of TCA cycle
-transketolation reaction of HMP stunt pathway
• role in energy metabolism of most cells particularly
important in tissues of nervous system
• In thiamine deficiency, the activity of these two
dehydrogenase catalysed reaction is decreased,
resulting in decreased production of ATP
--thus result in impaired cellular function

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Fig: tca cycle

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Fig: HMP stunt Pathway

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Beriberi
• Beriberi is a nutritional disorder caused by a deficiency of vitamin B1 or
thiamine in the diet
• it is characterized by damage to nerves and heart with fatal outcomes
• Causes:
-Persons may become deficient in thiamine either by not ingesting enough
vitamin B-1 through the diet
- chronic alcoholism may cause decreased absorption of thiamine
- Prolonged diarrhea may impair the body's ability to absorb vitamin B1
-severe liver disease impairs its use
- infants nourishing from mother whose mother’s diet is inadequate in
thiamine
- rarely inherited

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Debilities of Beriberi
• Major target are peripheral nerves, heart, brain and
GI tract
• It gives 4 major syndromes:
1. Wet beriberi
2. Dry beriberi
3. Wernicke-Karsakoff syndrome
4. GI tract disorders

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1. Wet Beriberi
• Cardiovascular syndrome
• Beriberi heart disease
• Associated with peripheral vasodilation, leading to more rapid
arteriovenous shunting of blood, cardiac failure, pheripheral
edema
• Cardiac failure may be due to weaken cardiac muscle
• As a result of decreased release of metabolic energy in tissue
local vasodilation may occur
• Due to which the venous return of blood to heart may
increase to as much as two times.

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Vitamin B1 deficiency
Decreased metabolic energy in tissue
Local vasodilation
results
in
increased venous
return of blood
cause stunning of blood
Weaken cardiac muscle
results in cardiac failure
and peripheral edema

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2. Dry beriberi
• Polyneuropathy
• Usually symmetric and cause effects mainly in peripheral
nervous system
• Myelin degeneration and disruptions of axons involving
motor, sensory and reflex arcs resulting in progressive
sensory loss
• Lesions in peripheral nerves frequently cause them to
become extremely irritable, resulting in polyneuritis
• Serve cases can cause paralysis, muscle atropy, wrist and foot
drop and serve weakness

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3. Wernicke-Karsakoff syndrome
• Brain disorder
• Target system is central nervous system
• Encountered mostly in case of chronic alcoholism due to
-decreased absorption of thiamine from intestine
-less intake of diet
-liver storage is decreased
• CNS normally depends entirely on metabolism of carbohydrates for
its energy
• Utilization of glucose by nervous tissue may be decreased to 50-
60% and is replaced by utilization of ketone bodies derived from
fat metabolism.

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Wernicke-Karsakoff syndrome contd.
• Due to this the neuronal cells of CNS show chromatolysis i.e.;
dispersal or disintegration of microscopic structures within
nerve cells that normally produces protein. This is part of cells
response to injury.
• These changes may disrupt communication in many portions
of CNS
• This results in various neurological symptoms like psychosis,
confusion and hallucination

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4. GI tract disorders
• Due to lack of thiamine, smooth muscles and glands
of GI tract fail to derive sufficient energy from
carbohydrate metabolism
• This results in indigestion, serve constipation,
anorexia, and hypochlorhydria

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Treatment
• External thiamine supplements
• Taking diet rich in vitamin B1

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Conclusion
• Thiamine content of food may be lost due to
-polishing of rice
- overcooked food
-long preservation
• Lack of thiamine can be caused by
- malnutrition
- diet high in thiaminase rich food and food rich in anti-
thiamine factors
-chronic disease state like alcoholism, GI disease, persistent
vomiting

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• REFERENCES
• Park K (2000) Textbook of Preventive and Social
Medicine, M/s Banarsidas Bhanot Publishes,
Jabalpur, pp 412-13.
• Harvey R and Ferrier D (2011) Biochemistry, Wolters
Kluwer Pvt. Ltd., New Delhi, pp 378-79.
• URL:
http//www.bettermedicine.com/article/beriberi
• URL:http://emedicine.medscape.com/article/116930

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THANK YOU

Vitamin b1(thiamine) and beriberi

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