History
500 BC Hippocrates liver for night-blindness 1757 Lind UK fresh fruit/veg cured British Navy from scurvy 1893 Eijkman in Java described and cured beri-beri (patients on polished rice) 1912 F. Gowland Hopkins found factors in milk needed for rat growth
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Deficiency Disease difficult concept at the time. diseases thought to be caused by a toxic factor, not the absence of a factor
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origin of names
McCallum and Davis (US), fat soluble factor (A) in butter and egg yolk, and heat labile factor (B),in wheat germ needed for the growth of young rats. subsequently found to be mixtures of vitamins.
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VITAMIN
A complex organic substance required in the diet in small amounts , compared to other dietary components such as protein carbohydrate and fat, and whose absence leads to a deficiency disease.
water/fat soluble
Water soluble: B group, C not stored extensively needed regularly generally not toxic in excess (within reason) Fat soluble: A D stored not absorbed easily not excreted easily may be toxic in excess (A, D) E K
In the West the main manifestation of thiamin deficiency is the 'Wernicke - Korsakoff syndrome', mainly associated with alcoholism.
In the USA, alcohol related thiamin deficiency is the 3rd commonest cause of dementia
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Foodstuffs deficient in the vitamin: polished rice, sugar, fat, refined and processed foods. Effective intake reduced by thiaminases (found in raw fish) and anti-thiamin factors found in coffee, tea.
Biochemical role:
As thiamin pyrophosphate (TPP) coenzyme e.g.
pyruvate p acetyl CoA pyruvate dehydrogenase complex deficiency results in accumulation of lactate in muscles
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Wernicke/Korsakoff syndrome
Wernicke's encephalopathy 1930s recognised as cerebral beri-beri confusion ,disorientation in space and time. progresses into: Korsakoff's psychosis loss of memory of recent events. mainly in alcoholics Alcohol leads to anorexia, inhibition of absorption of thiamin inhibition of the enzyme which converts thiamin into its active form TPP
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RIBOFLAVIN (B2)
UV sensitive, mainly in milk, usually associated with protein. Function As FAD and FMN in redox reactions. Deficiency Rare, except in alcoholics. Symptoms mild : cheilosis, angular stomatitis and cataracts. It is protein bound. diets adequate in protein will be adequate in riboflavin. In UK, low status in alcoholics, the elderly and some adolescents ( British schoolchildren diet survey). It is not toxic in excess.
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NIACIN
Nicotinic acid or nicotinamide Function As NAD and NADP in redox reactions. Sources of niacin: in cereals in small amounts, its bioavailability is low. high protein diets have no requirement for niacin can be formed from tryptophan.
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Deficiency
Pellagra maize eating people in Europe and USA. fatal if severe Dermatitis photosensitive (Casal's necklace). Diarrhoea Dementia
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PYRIDOXINE (B6)
Pyridoxine, pyridoxamine, pyridoxal Function Active form: pyridoxal phosphate essential for amino acid metabolism (transaminations, deaminations etc.). and haem synthesis Deficiency commonest is secondary, caused by the presence of antagonistics Isoniazid, in treatment of TB combines with PP and renders it unavailable. Patients given B6 supplements. no evidence that oral contraceptives increase requirement
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Therapeutic uses/Toxicity
treatment of seizures, Down's syndrome autism, no good reason! pre-menstrual tension syndrome (PMS) Women, self-medicating for PMS, taking 500-5000 mg /day have shown peripheral neuropathy within one to three years.
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Folate
It is a carrier of 1-C fragments e.g.: - CHO N5 formyl THFA - CHO N10 formyl THFA - CH! NH N5 formimino ! CH N5,10 methenyl - CH2 N5,10 methylene - CH3 N5 methyl
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Metabolic functions:
Folate 1-C transfer reactions in: purine and pyrimidine synthesis amino acid metabolism e.g. homocysteine to methionine B12 conversion of homocysteine to methionine in branched chain amino acid metabolism
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Neurological changes: Inadequate myelin synthesis. Symptoms: numbness fingers hands and forearms, tingling hands and feet, moodiness, depression. nerve lesions.
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PANTOTHENIC ACID
Source Ubiquitous Function Component of the coenzyme-A (CoASH) in the metabolism and transfer of carbon chains e.g. fatty acid oxidation Deficiency Rare
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BIOTIN
Source Widely distributed sufficient quantities provided by intestinal bacteria Function: Prosthetic group for carboxylations pyruvate p oxaloacetate acetyl CoA p malonyl CoA Deficiency Rare on a normal diet unless eating raw egg whites.
VITAMIN C (ascorbic acid) Sources Citrus fruits, tomatoes, berries. Function An anti-oxidant nutrient
Hydroxylation of proline and lysine in collagen formation. maintains the Fe(II) in proline and lysine hydroxylase active state. absorption of dietary Fe from the stomach Possibly, in vivo, as an anti-oxidant to protect vitamins A, E, K from oxidation
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Deficiency Scurvy The well fed human body has a 6 month store of vitamin C Signs of scurvy after three months on vitamin C free diet. impaired wound healing, haemorrhages and anaemia Vitamin C status in the UK Low status in the elderly, in alcoholics and in adolescents especially on 'junk' food. Smokers need twice the normal intakes (80 mg/day) as the turnover of ascorbic acid is greatly increased by smoking.
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Megadoses:
Benefits uncertain and under review: cholesterol turnover, immune function, male fertility, cancer prevention, Se and Fe utilisation, physical working capacity. cold: No evidence that megadoses have an effect Heart disease, cancer, eye diseases- no clear pattern Risks of megadoses: Oxalate (major metabolite)) kidney stones in susceptible individuals, diarrhoea, systemic conditioning
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VITAMIN A
Sources as retinol Animal liver and fish liver oils, whole milk and egg yolk plant carotenoids (mainly F carotene) Green/yellow/ orange vegetables and fruit. Absorption Carotenoids are cleaved to 2 retinol molecules conversion is inefficient, ratio carotene : retinol not 1:2 but 6:1
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Active forms retinoic acid acts as a hormone retinal in vision (F carotene antioxidant) Functions control of protein synthesis retinoic acid affects synthesis of proteins involved in cell growth and differentiation.
in vision best understood function at low light intensity participates in conversion of light energy to impulses in the optic nerve in the rod cells of the retina
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Deficiency rarely seen in developed countries, but common in developing countries e.g. India & SE Asia Usually associated with inadequate protein diets.
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Night blindness (role in vision), followed by: progressive keratinisation of the cornea (xerophthalmia), and finally keratomalacia and irreversible blindness.
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Toxicity/Teratogenicity
Dermatitis, hair loss nausea, fracture of long bones. unlikely with normal sources but possible with supplements e.g. for acne or colds. In pregnancy not recommended Pregnant women should not take supplements or eat liver regularly.
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VITAMIN E
Source Vegetable oils especially wheat germ oil, nuts, green vegetables. most potent: E-tocopherol naturally occurring ANTIOXIDANT. Function Prevents oxidation of unsaturated/poly-unsaturated fatty acids (PUFA) in cell membranes and circulating lipoproteins. PUFA are particularly susceptible to attack by free radicals. Destruction disrupts membrane structure and cell integrity. A chain reaction which vit E can terminate
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Deficiency:
Virtually unknown except in premature, low birth weight infants. vitamin E does not cross the placenta easily; human milk is not a good source of vitamin E. Haemolytic anaemia due to fragility of red cell membranes is characteristic. Vitamin E is now included in infant formulae
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Requirements difficult to establish, likely to be higher with high PUFA intake. A protective effect against cardiovascular disease and cancer? Vitamin E is thought to protect fatty acids and apoprotein B in LDL from oxidative damage.
VITAMIN D
a group of similar compounds. Vitamin D2 (ergocalciferol) derived from ergosterol widely found in plants, fungi and moulds. Cholecalciferol (vitamin D3) occurs naturally in animals.
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Sources: Milk and dairy products, fortified margarine, eggs. Cholecalciferol formed in skin by UV light on 7dehydrocholesterol, Function maintains correct levels of calcium and phosphate in the blood so that proper mineralisation of bone is achieved.
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Deficiency
Rickets in children and osteomalacia in adults Rickets mineral : matrix ratio decreases in bone bending of long bones and kyphosis.
Osteomalacia There is muscle weakness, bone pain and decalcification of long bones nearly always due to Vit D deficiency and rarely a calcium deficiency Borderline cases of deficiency common in the UK especially in the elderly and also in Asian children and women especially in the north of England and Scotland
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Toxicity
Excessive consumption of vitamin D is toxic. Hypercalcaemia, calcification of soft tissues Can be fatal
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VITAMIN K
Sources A considerable amount from the bacterial flora of the jejunum and ileum. Human milk has a low vitamin-K content infants may have marginal insufficiency the neonatal gut is sterile. Deficiency Blood clotting is defective. Deficiency resulting in increased blood clotting time is rare except: In long term antibiotic therapy
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haemorrhagic disease of the new-born poor placental transfer and no gut flora. affected babies develop intracranial haemorrhages. 50% die and the other 50% have neurological malfunction. In the UK babies have been given vitamin K at birth since the 1950s.
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