Nutritional basis of Anaemia slides.ppt

Dr M Chopra School of Pharmacy and Biomedical Science St Michael’s Building Lecture Outline Overview of various causes of anaemia with emphasis on the nutritional aspects of anaemia. Discussion of mechanisms that lead to nutrition and infection related anaemia Factors that influences bioavail...

Dr M Chopra School of Pharmacy and Biomedical Science St Michael’s Building Lecture Outline Overview of various causes of anaemia with emphasis on the nutritional aspects of anaemia. Discussion of mechanisms that lead to nutrition and infection related anaemia Factors that influences bioavailability of nutrients important for red blood cell synthesis and integrity Factors contributing to Anaemia Impaired synthesis of cells Erythrocyte loss/Blood Loss Interference by Disease (Inflammation, Renal disease) Poor Nutrition (Protein, Iron and vitamins B6, B9 and B12 are the most important) Depresses plasma retinol Thurnham & Clewes (2005) Infection in the etiology of anemia, In ‘Nutritional Anemia’. Eds Kraemer & Zimmerman. Chap 15 pp 231-256Sight & Life Press:Basel. Poor Nutrition and Anaemia Protein energy malnutrition Iron Vitamins B2 and B6 Vitamins B9 and B12 Closely related vitamins that depend on each other for activation. Blood symptoms of their deficiency are large immature red blood cells. Other micronutrients likely to be important Vitamin E Vitamin C Copper Anaemia classification (Gavin’s lecture) Macrocytic, normo/hypochromic Megaloblastic ( vitamins B9 and B12 deficiency)  Non-megaloblastic  Normocytic, normochromic  Anaemia of chronic disease Microcytic, hypochromic Iron deficiency  Thalassaemia  Protein Energy malnutrition and Anaemia With low protein levels: Haemoglobin synthesis is affected More prone to infections Ineffective erythropoiesis Cell renewal/cell proliferation is affected Prevalent in malnourished children, elderly and anorexic individuals Learning Outcomes After this session, you should have an understanding of: Diet sources of iron and factors that can affect bioavailability of iron consumed from diet. Various functions of iron. Factors that influence iron levels in the body after ingestion. Iron 70 Kg man - ~ 4g of Iron 60-70% is in Haemoglobin and Myoglobin Iron porphyrin complex in Haemoglobin transport O to tissues 2 Iron porphyrin complex in myoglobin (an O store for muscle 2 contraction) iron is in Ferritin, haemosiderin, transferrin, the cytochromes, catalase, and iron-sulphur proteins of respiration. Remaining Recommended daily intake is 8 mg for men and 15 mg for women during child bearing age Iron Functions Nearly every microorganism needs Iron for Growth and Metabolism •Haem centers (haemoglobin, myoglobin) •Enzymes DNA replication (ribonucleotide reductase) Respiratory chain (cytochrome C proteins) Antioxidants (peroxidases, catalase) Factors that can influence Iron levels in blood following its ingestion Food source: Animal vs plant Factors that affect its absorption Metabolic need of the body Exposure to infection/inflammation Iron from Diet Iron status is influenced by: Dietary Intake, Absorption There are two forms of dietary iron: Haem (Fe2+) Non-haem (Fe3+)  Meat, fish and poultry: major source (haem iron more bioavailable).  Protein rich foods i.e. legumes, beans and eggs are also a good source.  Wholegrain, enriched breads and cereals (contain fibre that might inhibit absorption).  Dark green vegetables (broccoli, spinach) and some dried fruits - (non-haem iron – less bioavailable) Fe2+ Form in which iron is Absorbe reduced d Fe3+ Storage oxidised iron, transport iron Iron and Anaemia Two important factors that play a role in Iron deficiency associated anaemia are: Iron status (diet, bioavailability) Inflammation Absorption of Iron 1 Special proteins – absorption of iron from food – mucosal ferritin, mucosal transferrin, blood transferrin. Main regulation at absorption of iron. Three mechanisms regulate iron absorption: •Dietary regulator – a short term increase in dietary iron is not absorbed as the accumulated iron in mucosal cells inhibits further absorption. •Store regulator – as body stores drop, mucosa is signalled to moderately increase absorption. •Erythropoitic regulator – in response to anaemia, erythroid cells Iron absorption Physiological factors controlling iron absorption  Iron in intestinal mucosa  Body iron stores (as indicated by s.ferritin) [Fe absorption only increased if serum ferritin <25 µg/L]  Rate of erythropoiesis  Tissue hypoxia  Growth and pregnancy increase absorption  Gastric hydrochloric acid stimulates release of Fe from food  Slow stomach emptying promotes iron absorption Absorption of Iron 2 • Reduced form (Ferrous, Fe2+) is absorbed better. • Vitamin C enhances non-haem (Fe3+) iron absorption by keeping it in the reduced state. • Animal products - Meat, fish and poultry contain well-absorbed haem (Fe2+) iron, but also a factor (MFP factor) that promotes the absorption of non-haem (Fe3+) iron from other foods eaten in the same meal. • Fibre, phytates, oxalates, calcium, phosphorus, tannic acid inhibit iron absorption. Iron distribution and metabolism in the body RE = reticuloendothelial cells Fairweather-Tait (1995) Iron biochemistry, In ‘Iron – Nutritional and Physiological Significance. Brit Nutrition Foundation, TJ Press; Infection and Anaemia Anaemia can occur due to: Iron-deficiency Chronic infection/inflammation  It is often difficult to know the proportion of anaemia caused by dietary iron deficiency or by inflammation. o In developing countries it is estimated that iron deficiency and inflammation each contribute 50% of anaemia. o In industrialised countries, it is difficult to know the proportions of anaemia due to dietary iron deficiency and to inflammation. o The prevalence of obesity in industrialised countries is rising and obesity increases the risk Inflammation and Iron metabolism Iron stores & Inflammatio n (+) Dietary Iron (-) Duodenal enterocytes 1-2 mg/d Circulating iron Hepcidin (-) Hypoxia, Anaemia & Erythropoiesi s (-) R.E, macrophages Senescent Red cells 20-25 mg/d Iron deficiency diseases/conditions Iron Deficiency and Behaviour Certain mood changes occur when iron levels begin to drop long before red cells are affected and anaemia is detected. - iron deficiency impairs oxidation of pyruvate - leading to reduced energy – unmotivation, apathy. • Iron Deficiency and Pica Iron deficiency can lead to craving for ice, clay, paste and other non-food substances. Clay inhibits iron absorption. Iron Toxicity  Primary haemochromoatosis – excessive iron storage/enhanced iron absorption – caused by genetic defect, increased deposition of haemosiderin.  Secondary Cause: – Iron Overload – Repeated blood transfusion, massive doses of iron- haemosiderosis. - Iron overload is characterised by tissue damage and infections are likely because bacteria thrive on iron rich blood. - Alcohol damages intestines, therefore iron overload symptoms are more severe in alcohol abusers iron overload aggravates the risk of diabetes, Untreated liver disease, cancer and heart disease. Iron Deficiency and Anaemia • Anaemia and Iron deficiency: - Not necessarily the same thing Learning Outcomes After this session, you should have an understanding of: The dietary sources of B vitamins that play a role in cell differentiation and growth. Integration between B vitamins in relation to cell differentiation. Factors that influence B vitamin levels in the body after ingestion. Pros and cons of using supplements that can affect cell differentiation function of vitamin B9. Vitamins B2 and B6 Synthesis of globin protein and iron metabolism. There are also suggestions that vitamin B2 (riboflavin) deficiency may alter iron metabolism through reduction in iron absorption (increased intestinal loss of iron) and/or impaired utilisation of iron for haemoglobin synthesis (Powers HJ. Am J Clin Nutr 77, 2003). Dietary source of riboflavin (B2): Dairy products. Vitamin B6 is required as a coenzyme for the synthesis delta-aminoevulinic acid which is the rate-limiting step in the synthesis of haem. Dietary sources of vitamin B6: Plants as well as animals. Vitamin B6 • Vitamin B6 (pyridoxine) is watersoluble. • Needed for more than 100 enzymes that play roles in protein metabolism. • Deficiency can result in anaemia but is rare. • Found in a wide variety of foods. important active form of enzyme • The Food Sources: cofactor is pyridoxal phosphate (PLP). • Pyridoxine: Plant source i.e. bananas, beans, peas, walnuts Vitamin B9 (folate/folic acid) and Vitamin B12 Interaction • Both vitamins play an important role in cell differentiation. • Vitamins B2 and B12 work together to produce the active form of vitamin B 9 (tetrahydrofolate production). • Tetrahydrofolate (THF) in the form of 5,10- methylene tetrahydrofolate is necessary for the DNA synthesis (thymidine synthesis). • Deficiency of both B9 and B12 impairs cell division in bone marrow while RNA and protein synthesis B9 Active Form B9 B2 B9 Inactive form 5,10-Methylene tetrahydrofolate (TH4) is required for the synthesis of nucleic acids, while 5-methyl TH4 is required for the formation of methionine from homocysteine by the vitamin B12-dependent enzyme, methionine synthase. Methionine, in the form of Sadenosylmethionine, is required for many biological methylation reactions, including the methylation of DNA. Vitamin B12 deficiency traps folate in a form that is unusable by the Functions/uses of Vitamin B9 ((folate/folic acid) Main function Functions as a coenzyme in DNA an RNA synthesisimportant for healthy cell division & replication. Plays a role in the formation of new cells o Needed by body for the production of healthy red blood cells. o Strengthens immunity by aiding in the proper formation and functioning of white blood cells.  May also help with depression and anxiety. Lowers homocysteine levels in blood. Sources of Vitamin B9  Natural source  Lentils and beans Green leafy vegetables (sprouts, spinach, green beans, peas, okra, asparagus)  Fruits–especially oranges  Milk and dairy products, meat (liver)  Yeast extract  Fortified foods: fortified breakfast cereals, bread, yeast extract  Supplements  RDI – 200 g/day (400 g/d for pregnant women). Bioavailability from fortified foods and supplements is believed to be double of that from natural sources –monoglutamate form.  Absorption takes place in small intestines (folate conjugates hydrolysed by pancreatic enzyme conjugase), high in slight acidic areas, low in alkaline areas. Bioavailability from milk is high (protein- Deficiency of Vitamin B9  Deficiency impairs cell division and protein synthesis Deficiency may develop due to: • Inadequate intake • Increased alcohol consumption • Impaired absorption • Increased metabolic need • Drugs – anticancer, aspirin, antacids  Deficiency may lead to birth defects in one’s offspring's On stopping foods containing B12, deficiency takes years to develop because body recycles much of its B12. In B12 deficiency - Bone marrow makes fewer red blood cells and many of the cells that are formed are large and immature resulting in megaloblastic anaemia. Two main diseases in humans due to B12 deficiency : Megoblastic Anaemia Neuropathy Vitamin B12 contains cobalt, therefore is called cobalamin. Sources: Exclusively synthesised by bacteria; Meat, eggs and dairy products are the best source Fermented soy products, seaweeds, and algae such as spirulina suggested to contain significant B12 (may not be bioavailable) Bioavailability: Absorption requires Treatment of vitamins B9 and B12 deficiency Appropriate dietary recommendation or supplementation needs to be considered. In case of B12 deficiency, if the diet regime and supplements are not effective, patients are given 1000 µg dose three times a week for 2 weeks to build up the tissue stores followed by intramuscular administration of 1000 µg vitamin B12 every 3 months. Some Cautionary notes  Anaemia symptoms due to B9 deficiency are similar to B12 deficiency.  Vitamin B9 supplements can cure the symptoms of anaemia caused by vitamin B12 deficiency, but is ineffective against vitamin B12 deficiency-related nerve damages.  Folic acid can mask a vitamin B12 deficiency causing certain nerve ailments to progress to an irreversible stage • Due to conflicts with vitamin B12 deficiency, folic acid in high quantity should be avoided unless vitamin B12 deficiency is completely ruled out. • Folic acid is suggested to have masking effect on vitamin B12 deficiency at intake of > 1000 μg/day, Too much use of Vitamin C can destroy vitamin B12 and cause red blood cell destruction. Vitamins B9 and B12 excretion enhanced at megadoses of vitamin C. Session 4 Outline At the end of this session, you should develop an understanding of: Relatively less frequent but still important causes of Nutrition related anaemia  Function • Antioxidant  Deficiency •Anaemia •Infertility Principal Source • Fats and oils • Some processed foods (fortified cereals) Nuts, in grains, green leafy vegetables • Intake Suggested UK 1 mg of α –Tocopherol = 10 mg α –Tocopherol equivalent for males 1.49 IU of Natural 2.2 IU of Synthetic  Best known function is to prevent the oxidation of double bonds in the hydrocarbon tails of lipids. Deficiency can cause: •Damage to red blood cells (erythrocyte haemolysis), shortened red blood cell life spanAnaemia. • Fertility (both in men and women), menstrual problems, uterine degeneration, sperm motility affected by Vitamin E deficiency. Bioavailability of vitamin E contd  Natural vitamin E is more bioavailable than synthetic.  Elimination of synthetic vitamin E occurs at a faster rate than natural. Vitamin C deficiency and Anaemia Too high and low vitamin C can influence anaemia. Non-haem iron absorption is dependent on vitamin C. Common in those whose main dietary source of iron is plant foods. Foods containing high vitamin C create environment in stomach which is favourable for iron absorption. Vitamin C converts Fe3+ to Fe2+ and latter is more easily absorbed. Copper deficiency and Anaemia Rare Copper cofactor for ferroxidase II, which oxidizes iron, allowing it to be mobilized and transported from hepatic stores to the bone marrow for use in erythropoiesis. In copper deficiency, iron is not mobilised from liver to bone marrow therefore the process of erythropoiesis is affected leading to anaemia. Zinc and Anaemia Zinc deficiency as well as taking too much zinc can cause anaemia. Zinc required for cell proliferation and therefore will affect RBC synthesis. Taking too much zinc can influence iron absorption and vice versa. Anaemic individuals should consume diet high in both iron and zinc. Zinc dietary sources are:Meat, fish, poultry, shellfish, eggs, legumes. In Summary There are several causes of Anaemia. They all need to be considered to determine the underlying cause so that appropriate treatment can be considered. Blood samples should be tested to determine the cause and tested again following the treatment. Several nutrients are important for the red blood cell formation and stability. Dietary sources of these nutrients are a better option than taking the supplements (unless under medical supervision). Individuals at risk of Nutrition Anaemia Your Task When, How and Who can be at risk of developing Nutrition related anaemia