Vitamins Part A 2023 PDF

Vitamins MBBS stage 1 Nutrition and Metabolism part A Despo Papachristodoulou How do we know how much of a nutrient we are taking in? Look at food tables Look at the side of the package We do not know We assume that we are taking enough if we are not ill...

Vitamins MBBS stage 1 Nutrition and Metabolism part A Despo Papachristodoulou How do we know how much of a nutrient we are taking in? Look at food tables Look at the side of the package We do not know We assume that we are taking enough if we are not ill  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 The 'Vitamine Theory' of Disease in 1912 Hopkins and Funk – specific diseases e.g beri-beri, scurvy, rickets caused by lack of specific nutritional factors – Funk introduced the term vita-mine (vital amine). – Deficiency Disease difficult concept at the time. diseases thought to be caused by a toxic factor, not the absence of a factor  origin of names McCallum and Davis (US), fat soluble factor (A) in butter and egg yolk, heat labile factor (B),in wheat germ needed for the growth of young rats. subsequently found to be mixtures of vitamins.  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 E K stored not absorbed easily not excreted easily may be toxic in excess (A, D)  THE B GROUP OF VITAMINS ALL B VITAMINS ACT AS CO-ENZYMES IN METABOLIC PATHWAYS THIAMIN (B1) Isolated in 1926 as the anti beri-beri factor. Deficiencies first treated in 1897 by Eijkman, working in Java with patients whose diet consisted mainly of polished rice. In the 2Ist century deficiency still in Thailand, the Philippines, India and some areas in Japan (especially infantile beri-beri). Wernicke’s encephalopathy/Korsakoff’s psychosis In the West main manifestation of thiamin deficiency 'Wernicke - Korsakoff syndrome' mainly associated with alcoholism. In the USA, alcohol related thiamin deficiency is the 5th commonest cause of dementia  Good sources/ Requirement : whole grain, pork, poultry, fish, vegetables, dairy produce. Foodstuffs deficient in the vitamin: polished rice, sugar, fat, refined and processed foods. DRV 1.4 mg / day ( male) 1.0 mg / day (female) 0.5 mg / day / 1000 kcal Requirement high if carbohydrate intake is high Note thiaminases (raw fish) and anti-thiamin factors (coffee, tea).  Biochemical role: As thiamin pyrophosphate (TPP) ‘coenzyme’ e.g. pyruvate acetyl CoA pyruvate dehydrogenase complex deficiency results in accumulation of lactate in muscles  Presentation of thiamin deficiency: Beri-beri 1. Infantile beri-beri Sudden onset, cardiovascular symptoms 2. Acute cardiac beri-beri congestive heart failure, enlarged heart, liver, engorged neck veins sudden heart failure 3. chronic dry beri-beri symmetrical ascending peripheral neuropathy weakness, numbness, ataxic gait, painful extremities wet beri beri Dry beri beri  Wernicke/Korsakoff syndrome Wernicke's encephalopathy 1930’s recognised as cerebral beri-beri confusion , ataxia, polyneuropathy ,disorientation in space and time. If untreated, progresses into: Korsakoff's psychosis principal feature: loss of memory of recent events. W/K syndrome is seen mainly in alcoholics Alcohol leads to anorexia, inhibition of active transport (absorption) of thiamin from the intestine, inhibition of the enzyme which converts thiamin into TPP Korsakoff’s psychosis  Alcoholics suffer many B vitamin deficiencies because: may have adequate energy intake but as 'empty calories' from alcohol inadequate levels of vitamins and other nutrients. GI tract malfunctions are common. Cirrhotic liver affects storage, transport and metabolism of many vitamins. storage and transport of fat soluble vitamins ,e.g. vitamin A, may be impaired  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.  NIACIN Nicotinic acid /nicotinamide : vitamers (different structural forms of a vitamin). 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.  Deficiency Pellagra maize eating people in Europe and USA. fatal if severe Dermatitis photosensitive (Casal's necklace). Diarrhoea Dementia  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  Therapeutic uses/Toxicity treatment of seizures Down's syndrome autism, pre-menstrual tension syndrome (PMS) (with variable success) Women, self-medicating for PMS, taking 500-5000 mg /day have shown peripheral neuropathy within one to three years.  FOLATE AND VITAMIN B12 1926 Minot and Murphy Nobel prize for Medicine for treatment of pernicious anaemia with raw liver (oral liver therapy). Function Vitamin B12 (cobalamin) a carrier of methyl groups in mammalian metabolism Folate structure and function: carrier of 1C units Active form : tetrahydrofolate, dihydrofolate reductase important in maintenance of this form.  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  Absorption of B12 /Folate B12 only in animal tissues. Vegan diets, no B12. DRV: 1 g /day binds to glycoprotein secreted from gastric cells, the intrinsic factor needed for absorption and transport of B12. commonest cause of pernicious anaemia is lack of intrinsic factor. Pharmacological doses absorbed by diffusion along the entire length of the small intestine, only 1% is absorbed in this way, but it enables oral therapy Folate mainly in green vegetables, liver and whole grains. DRV 50 g / day normal serum levels are 5 - 15 ng/ml  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  folate dihydrofolate methionine DHF reductase tetrahydrofolate homocysteine methotrexate B12 pool of 1-C THF derivatives all interconvertible except Me THF MeTHF purines, pyrimidines amino acids  METHOTREXATE Used in Chemotherapy As immunosuppressant in autoimmune diseases Ectopic pregnancies  Megaloblastosis: Explanation of symptoms B12 and folate needed for thymidylate synthesis and  DNA B12 dependent methionine synthetase only means of Me THF return to the folate pool. B12 deficiency 'traps' THF in the Me THF form producing functional THF deficiency explains why haematological picture of B12 deficiency identical to folate deficiency. In both cases, lack of 5,10 methylene THF and hence lack of adequate DNA synthesis: haemopoietic cells die in bone marrow without completing cell cycle. Megaloblastosis: giant germ cells.  Neurological changes: Inadequate myelin synthesis. Symptoms: numbness fingers hands and forearms tingling hands and feet loss of position sense unsteadiness, ataxia, confusion, moodiness, depression. spinal cord, brain and peripheral nerve lesions.  Causes of deficiency: Inadequate intake, inadequate absorption B12 absent IF, defective IF, gastric atrophy, gastrectomy, coeliac disease (ileum) Crohn’s disease (terminal ileum most commonly affected) folate malabsorption, tropical sprue, drugs e.g. barbiturates and anti-convulsants, ethanol, ?oral contraceptives.  Folate and Neural tube defects UK : one of the world’s highest rates of neural tube defects. 1991 blind trial folate supplementation or mixture of other vitamins around conception time ?could prevent neural tube defects (anencephaly, spina bifida, encephalocele) in women who already had one affected pregnancy 72 % reduction in the incidence of neural tube defects in the groups supplemented with folic acid. In the UK all pregnant women attending ante-natal clinics are routinely prescribed folate supplements.  Folate, B6 and B12 and cardiovascular mortality Hyperhomocysteinaemia and CVD Some studies show link between high homocysteine conc and some not Is it a link or a cause? Some studies show lower risk of CVD with high dose supplements of the B’s and some do not.  Folate, B6 and B12 and Alzheimer’s certain B vitamins can halve the rate of brain shrinkage in elderly people who suffer from mild memory problems, an Oxford University study has shown. Sep 2010. 168 volunteers aged 70 or over with mild memory problems, half of whom took high dose B vitamin tablets for two years and the other half a placebo tablet. The researchers assessed disease progression in this group by using MRI scans to measure the brain atrophy rate over a two-year period. on average the brains of those taking the folic acid, vitamin B6 and B12 treatment shrank at a rate of 0.76% a year, those in the placebo group had a mean brain shrinkage rate of 1.08%. People with the highest levels of homocysteine benefited most  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  BIOTIN Source Widely distributed; peanuts, chocolate and egg yolk normally sufficient quantities provided by intestinal bacterial synthesis. Function: Prosthetic group for carboxylations pyruvate oxaloacetate acetyl CoA malonyl CoA Deficiency Rare on a normal diet unless eating raw egg whites. Long term antibiotic therapy resulting in sterilisation of the abdominal tract is the commonest cause of deficiency.