Thiamin Deficiency and Wernicke-Korsakoff Syndrome

Thiamin (Vitamin B1)

• Deficiency still present in Thailand, the Philippines, India, and some areas in Japan, particularly in infantile beri-beri.
• In the West, the main manifestation of thiamin deficiency is Wernicke-Korsakoff syndrome, mainly associated with alcoholism.
• In the USA, alcohol-related thiamin deficiency is the 5th commonest cause of dementia.
• Good sources of thiamin: whole grain, pork, poultry, fish, vegetables, and dairy produce.
• Foodstuffs deficient in thiamin: polished rice, sugar, fat, and refined and processed foods.
• Recommended daily intake: 1.4 mg/day (male) and 1.0 mg/day (female).
• Requirement increases with high carbohydrate intake.
• Thiaminases (raw fish) and anti-thiamin factors (coffee, tea) can reduce thiamin availability.

Biochemical Role of Thiamin

• Thiamin is converted to thiamin pyrophosphate (TPP), which acts as a coenzyme in pyruvate dehydrogenase complex.
• Deficiency leads to lactate accumulation in muscles.

Presentation of Thiamin Deficiency

• Beri-beri:
  • Infantile beri-beri: sudden onset, cardiovascular symptoms.
  • Acute cardiac beri-beri: congestive heart failure, enlarged heart, liver, and engorged neck veins.
  • Chronic dry beri-beri: symmetrical ascending peripheral neuropathy, weakness, numbness, ataxic gait, and painful extremities.
• Wernicke-Korsakoff syndrome:
  • Wernicke's encephalopathy: confusion, ataxia, polyneuropathy, and disorientation in space and time.
  • Korsakoff's psychosis: loss of memory of recent events.

Other B Vitamins

Riboflavin (B2)

• UV sensitive, mainly found in milk, and associated with protein.
• Function: as FAD and FMN in redox reactions.
• Deficiency: rare, except in alcoholics, with symptoms of cheilosis, angular stomatitis, and cataracts.
• Not toxic in excess.

Niacin (Vitamin B3)

• Viatmers: nicotinic acid and nicotinamide.
• Function: as NAD and NADP in redox reactions.
• Sources: cereals, with low bioavailability, and high protein diets that can form niacin from tryptophan.
• Deficiency: Pellagra, with symptoms of dermatitis, diarrhoea, and dementia.

Pyridoxine (Vitamin B6)

• Viatmers: pyridoxine, pyridoxamine, and pyridoxal.
• Function: as pyridoxal phosphate, essential for amino acid metabolism and haem synthesis.
• Deficiency: common, secondary, caused by the presence of antagonists, and can be treated with supplements.

Folate and Vitamin B12

• Function: as carriers of 1C units and methyl groups in mammalian metabolism.
• Active forms: tetrahydrofolate and pyridoxal phosphate.
• Deficiency: megaloblastosis, with symptoms of anaemia, numbness, tingling, and loss of position sense.
• Causes of deficiency: inadequate intake, inadequate absorption, and certain diseases or medications.

Methotrexate

• Used in chemotherapy, as an immunosuppressant in autoimmune diseases, and in ectopic pregnancies.
• Mechanism: inhibits dihydrofolate reductase, reducing folate availability.

Folate and Neural Tube Defects

• Supplementation with folic acid around conception time can prevent neural tube defects in women who have had a previous affected pregnancy.
• In the UK, all pregnant women attending ante-natal clinics are prescribed folate supplements.

Folate, B6, and B12 and Cardiovascular Mortality

• Hyperhomocysteinaemia may be linked to cardiovascular disease, but it is unclear whether it is a cause or a link.

Folate, B6, and B12 and Alzheimer's Disease

• High doses of B vitamins may halve the rate of brain shrinkage in elderly people with mild memory problems.