Vitamins (2023) PDF - Royal College of Surgeons in Ireland, Medical University of Bahrain

Royal College of Surgeons in Ireland Medical University of Bahrain Vitamins Salim Fredericks Learning objectives Describe the dietary sources and absorption of fat soluble vitamins Explain the function of each fat soluble vitamin in the body Describe the dietary source...

Royal College of Surgeons in Ireland Medical University of Bahrain Vitamins Salim Fredericks Learning objectives Describe the dietary sources and absorption of fat soluble vitamins Explain the function of each fat soluble vitamin in the body Describe the dietary sources and absorption of water soluble vitamins Explain the function of each water soluble vitamin in the body Discuss the effects and clinical signs of deficiency of vitamins Classification of vitamins Lippencott’s 28.1 DIETARY SOURCES OF FAT SOLUBLE VITAMINS Vitamin A = Retinoids Animal sources = Retinyl esters (REs) Vitamin D Fortified Foods Plant sources = beta carotene (pro-vitamin A) Vitamin E Vitamin K1 Vitamin K2: gut micro-flora in the large intestine ABSORPTION OF FAT SOLUBLE VITAMINS See GIHEP Lecture on Lipid Digestion in JC2 Absorption of fat soluble vitamins depends on: Normal pancreatic function Normal intestinal cells Bile salts to aid the emulsification of lipids in the gastrointestinal tract Vitamin A first vitamin to be discovered A group of related compounds - retinoids Animal sources: liver, dairy, egg yolk, fish oils Plant sources  e.g. β-carotene Functions – Retinaldehyde functions as light sensitive pigment in vision – in the protein rhodopsin ; – retinoic acid is gene regulator Retinol binding protein carries vitamin A in blood; this protein is bound to another protein, transthyretin Vitamin A Deficiency : night blindness; xeropthalmia; necessary for reproduction (spermatogenesis; prevent foetal resorption) Deficiency can result from protein malnutrition – lack of RBP Excess: Teratogenic in excess Chronic ingestion of large anmounts can cause liver and bone damage, alopecia, headaches.. RDA: 600-900 800 RAE/day [RAE (retinol activity equivalent) = 1µg retinol, 12 µg β- carotene] Vitamin D Hormone-like functions; regulation of calcium absorption and homeostasis; some immune functions Deficiency – rickets, osteomalacia Rickets – children, failure of bones to mineralize properly Osteomalacia – adults, demineralization of bone Sources – few natural – oily fish, eggs, liver. Fortified foods Can be synthesised in the skin under action of sunlight – deficiency in winter/North Vitamin D converted in the liver and kidney(PTH) to the active form, calcitriol Vitamin D toxicity – elevated plasma calcium - contraction of blood vessels. Calcification of soft tissues RDA? Skin synthesis. Adequate intake: for elderly is 5- 15 μg/day Vitamin E Group of 8 tocopherols Antioxidant in cell membranes Limits radical damage from oxidation of PUFA α-tocopherol (polyunsaturated FA) Deficiency: Dietary deficiency rare, but may be seen in fat malabsorption syndromes Premature infants; -(not easily transported across placenta) Anaemia due to fragility of RBC membrane. Experimental animals: testicular atrophy; skeletal & cardiac muscle affected; nervous system Sources : nuts, soy beans, vegetable oil, spinach Least toxic vitamin : 300 mg/day no ill effects Vitamin K Cofactor for enzymes involved in carboxylation of glutamate to γ-carboxyglutamate. Necessary for formation of prothrombin, factors II,VII, IX, X γ-carboxyglutamate found in other proteins e.g. osteocalcin in bone. Warfarin – vitamin K “antagonist”, used as anticoagulant. Sources : green leafy vegetables. Also synthesized by gut bacteria. RDA: not established Adequate intake: 60-120 ug/day Vitamin K deficiency Coagulation defects (‘koagulation’) Increased prothrombin time Osteoporosis: higher vit K correlates with greater bone density. Evidence that supplements improve bone health, esp. post- menopause Heart disease? Deficiency most often due to poor absorption in the gut rather than dietary inadequacy. - Coeliac disease, Crohn’s disease, fat malabsorption syndromes Recommended that newborns receive a single prophylactyic injection of vitamin K : (lack of gut bacteria, poor content of milk, possible poor placental transfer) DIETARY SOURCES OF WATER VITAMINS Vitamin B Complex Vitamin C ABSORPTION OF WATER SOLUBLE VITAMINS Have a look back at FUN6 Biological Membrane Structure Vitamin Absorption Thiamine Passive and active transport Riboflavin Passive down concnetration gradient Niacin Passive and faciltated diffusion Pantothenic acid Passive and active transport Pyroxidine Passive diffusion Biotin Faciliated diffussion* Folate Passive and active transport Cobalmin Requires intrinsic factor Ascorbate Active transport * Little is known about this Vitamin C – Ascorbic acid Main function is as reducing agent Co-enzyme in hydroxylation reactions Hydroxylation of proline and lysine in collagen Synthesis of carnitine Requirements: 45 – 90 mg/day Absorbed by specific transporter in intestine, maximum capacity 1-2 g/day – plasma levels do not increase significantly beyond 250 mg/day promotes absorption of iron in intestine Sources include blackcurrants, guava, citrus fruits Vitamin C – Ascorbic acid Deficiency : Scurvy. Sore spongy gums; loose teeth; fragile blood vessels, anaemia; fatigue Defective connective tissue - collagen Vitamin C and colds? – Some evidence that duration of colds is reduced but incidence is not VITAMIN B COMPLEX Thiamine: Vitamin B1 Riboflavin: Vitamin B2 Niacin: Vitamin B3 Pantothenic acid: Vitamin B5 Pyridoxine: Vitamin B6 Biotin: Vitamin B7 Folic acid: Vitamin B9 Cobalamin: Vitamin B12 Thiamine (B1) transketolase Co-enzyme for Pyruvate dehydrogenase (between glycolysis and Krebs cycle) α-ketoglutarate dehydrogenase (Krebs cycle) Transketolase – (pentose phosphate pathway) - Important role in energy metabolism/ NAD reduction/ Polished rice Switch from brown rice to white rice resulted in increase in incidence of beri-beri: this observation lead to the discovery of the vitamin Requirements : 0.5 mg/1000kcal for adults Lippencott’s 28.11 consuming more than 2000 k/cal; 0.8 – 1.0 mg for low energy intake RDA : 0.9-1.2 mg/day Thiamine Deficiency Beriberi Classified as “wet” or “dry” Wet symptoms:– – Signs of cardiac involvement: cardiovascular disease Dry Symptoms – peripheral and central neuropathies Wernicke-Korsakoff Syndrome (third most common cause of dementia in USA) Many sufferers are alcoholics Poor nutrition, decreased uptake of thiamine in GI, poor metabolism of thiamine Wernicke encephalopathy (WE):–Confusion–Ataxia–Paralysis of eye movement Korsakoff psychosis:– amnesia, confabulation Riboflavin (B2) Electron carriers in many redox reactions Deficiency Angular stomatitis; glossitis; dermatitis; conjunctivitis Riboflavin & opacity of the lens - GST necessary for clarity of crystallin, GST reductase sensitive to B2 deficiency [riboflavin deficiency offers protection against malaria] Milk and dairy products, eggs, meat, fish – (used as colouring agent) RDA: 0.9-1.3 mg/day Flavodoxin (a flavin-containing protein) Niacin - nicotinic acid (B3) Precursor for NAD, NADP Coenzymes in redox reactions Central roles in energy metabolism Can be synthesised from tryptophan (where Trp plentiful; this process is very inefficient) Inhibits lipolysis in adipose tissue  reduces LDL and VLDL. High doses 100x RDA used in treatment of type IIb hyperlipoproteinemia Sources: grains, milk, liver RDA: 12-16 mg/day (7 mg/ 1000kcal) Niacin deficiency Slower metabolism Decreased cold tolerance More severe deficiency: Pellagra Deficiency of Niacin and Tryptophan Deficiency syndrome : the three D’s : photosensitive Dermatitis; Diarrhea, Dementia (dementia may be due to Trp deficiency – reduced synthesis of serotonin) Maize – Niacin is unavailable and tryptophan is low; Pantothenate (B5) Functional moiety of Coenzyme A Central role in energy metabolism/ FA synthesis Eg, acetyl-CoA etc. Deficiency very rare – widely available in diet - “from everywhere” RDA : not established Adequate intake: 4-5 mg/day Pyridoxine (B6) ‘B6’ includes pyridoxine, pyridoxamine, pyridoxal Pyridoxal phosphate : coenzyme for many enzyme esp. some involved in amino acid metabolism e.g. aminotransferases Deficiency leading to clinical signs is very rare. In experimental animals, leads to increased sensitivity to steroid hormones. Some evidence that poor B6 intake is linked to poor breast cancer prognosis. Sources: esp raw food – heating causes reaction with lysine 13 μg/g dietary protein RDA 1-1.7 mg/day Biotin (B7) Coenzyme in carboxylation reactions e.g.: – Acetyl CoA carboxylase – Pyruvate carboxylase Widely available in diet, also available through synthesis by gut bacteria Deficiency rare. – – Dermatitis, Alopecia, glossitis, nausea, anorexia – Raw egg white contains avidin (a glycoprotein) which binds biotin v. tightly and can lead to deficiency when consumed in huge amounts (> 20/day) RDA : not established Adequate intakes 20-30 μg/day Folic acid (B9) Functions as 1-carbon carrier in synthesis of amino acids, purines and thymine Sources : fruits veg. supplements RDA : 300-400 μg/day Increase intake by 200 - 400 μg/day before conception. Needed very early in pregnancy Folate deficiency Macrocytic (megaloblastic) anaemia – Purine deficiency affects synthesis of DNA; this is noticed particularly in the bone marrow, a major site for synthesis of new cells resulting in abnormal development of blood cells In pregnancy: – Foetal neural tube defects / spina bifida – Low birth weight Vitamin B12 - Cobalamin Sources : only produced by bacteria/yeast. – animals obtain it from their natural flora or other animals. Liver, meat, milk, eggs Absorption of B12 Requires “intrinsic factor” – glycoprotein produced in stomach Complexes with B12  absorbed in lower ilium Significant amounts of B12 stored in body 4-5 mg. – a few years supply Absorption, transport, and tissue utilization of vitamin B. 12 IF, Intrinsic factor; TC II, transcobalamin II. Vitamin B12 - Cobalamin Cofactor for: Leucine aminopeptidase Methylmalonyl-CoA mutase Methionine synthase (folate connection) - Involved in transfer of methyl (CH3) groups pernicious anaemia : Deficiency : megaloblastic anaemia + subacute combined Megaloblastic anaemia – due to degeneration of the spinal cord folate deficiency Neurological effects : demyelination, nerve cell death. numbness, “subacute combined degeneration of spinal cord” RDA: 1.4 – 2.4 μg/day Vitamin B12 - Cobalamin Deficiency can be due to: Dietary deficiency rare (but seen in vegans??) Intestinal disease - lack of absorption in lower ilium Bacterial Overgrowth some intestinal bacteria require B12 for growth – overgrowth may interfere with absorption Gastric malfunction e.g. autoimmune disease, malignancy, gastrectomy - no intrinsic factor Summary of vitamins