8. MBCHB_NUTRITION AND FAT SOLUBLE VITAMINS_2023 NOTES_NoCopy.pdf

THE UNIVERSITY OF ZAMBIA SCHOOL OF MEDICINE PHYSIOLOGICAL SCIENCES DEPARTMENT NUTRITION AND FAT SOLUBLE VITAMINS Mwale Nicholas K.(PhD) [email protected] Conference Room, Adult Extension Studies Building, Ridgeway Campus...

THE UNIVERSITY OF ZAMBIA SCHOOL OF MEDICINE PHYSIOLOGICAL SCIENCES DEPARTMENT NUTRITION AND FAT SOLUBLE VITAMINS Mwale Nicholas K.(PhD) [email protected] Conference Room, Adult Extension Studies Building, Ridgeway Campus 1  OUTLINE OBJECTIVE of the topic: Describe normal nutrition and deviations from the normal state which can lead to diseases. NUTRITION – Definition – Importance of Nutrition Importance of food related to death Factors that contribute to death – Classification of Nutrients – Why we eat what we eat? – Dietary Reference Intakes – Dietary carbohydrate – Dietary fats – Dietary proteins – Nitrogen balance – Fuel stores VITAMINS – Overview – Fat-soluble vitamins A,D,E,K – Water-soluble vitamins Thiamine (Vitamin B1), Riboflavin (Vitamin B2), Pantothenic acid (Vitamin B5), Niacin (Nicotinic acid B3), Pyridoxine (Vitamin B6), Biotin (Vitamin B7), Cobalamin (Vitamin B12), Folic acid (pteroylglutamic acid B9) Vitamin C 2 Dr. Mwale, 2023  NUTRITION 3 Dr. Mwale, 2023  3. CLASSIFICATION OF NUTRIENTS. Nutrients are carbohydrates, proteins, lipids, vitamins, minerals and water. Various Classifications: TYPE 2: Classification MACRONUTRIENTS: carbohydrates, proteins, lipids, and water (required in larger amounts) MICRONUTRIENTS: vitamins, minerals (required in lesser amounts) ENERGY YEILDING NUTRIENTS/ENERGY CONTENT OF FOOD: Carbo: 1g=4kcal Prot: 1g=4kcal Lipids: 1g=9kcal Alcohol: 1g=7kcal (not a nutrient, is toxic) What is the total energy in 10g of carb, 5g of protein and 2g of fats?4 Dr. Mwale, 2023  4. WHY WE EAT WHAT WE EAT? Some: 1. Social factors -availability (wedding), -economical (money), -convenience (fast foods) 2. Behavioural factors -emotions(boredom, stress) -value (religion) -body image 3. Genetics? Find out what this is about 4. Personal preference - Taste (sweet vs salty food) -Upbringing -Habit -View of food 5 Dr. Mwale, 2023  5. DIETARY REFERENCE INTAKES (DRI). Refers to different reference of the intakes of nutrients: 1. Estimated Average Requirement (EAR) -Average amount sufficient for half the population (doesn’t meet the req.) Eg Joe req. 200kcal, Biden req 300kcal; average- 250kcal ????? 2. Recommended Dietary Allowance (RDA) -Meets the needs of 98% of population. -Based on scientific evidence; Calculated from double EAR. 3. Adequate Intake (AI) -Doesn’t meet the needs as evidence is on- going.Once conclusion made it becomes RDA 4. Tolerable Upper Intake Levels (UL) -Maximum consumption before it becomes toxic. -This helps against over-consumption. 6 Dr. Mwale, 2023  DIETARY REFERENCE INTAKES cont... 6. Estimated Energy Requirement (EER) -Amount of calories needed for daily function ie -vital functions of body (breathing, digestion) -physical activities (walking, exercises) -This maintains energy balance (calories consumed =the energy expended) in a healthy adult of a defined age, gender, and height whose weight and level of physical activity are consistent with good health. NOTE 1. Differences in the genetics, body composition, metabolism, and behavior of individuals make it difficult to accurately predict a person’s caloric requirements. 2. As a general guide; -very active adults require 40 kcal/kg/day to maintain body weight -moderately active adults require 35 kcal/kg/day to maintain body weight -sedentary adults require about 30 kcal/kg/day to maintain body weight 7 Dr. Mwale, 2023  Note cont... 3. To stay in energy balance, we must, on average, consume an amount of food equal to our daily energy expenditure (DEE). -The daily energy expenditure (DEE) = the energy to support our basal metabolism (basal metabolic rate or resting metabolic rate) and our physical activity, + the energy required to process the food we eat (diet-induced thermogenesis (DIT) or thermal effect of food). It can be summarised thus: Daily energy expenditure= RMR(or BMR) +Physical Activity +DIT where RMR is the resting metabolic rate; BMR is basal metabolic rate; DIT is diet-induced thermogenesis. 8 Dr. Mwale, 2023  6a) BASAL METABOLIC RATE OR RESTING METABOLIC RATE It is a measure of the energy required to carry out normal body functioning of the lungs, kidneys and brain, the pumping of the heart, the maintenance of ionic gradients across membranes, the biochemical reaction pathways, maintenance of cellular integrity, etc. Factors Affecting BMR Expressed per kg Body Weight 1. Gender (males higher than females) 2.Body temperature (increased with fever) 3.Environmental temperature (increased in cold) 4. Thyroid status (increased in hyperthyroidism) 5. Pregnancy and lactation (increased) 6. Age (decreases with age) A rough estimate of the BMR may be obtained by assuming it is 24 kcal/day/kg body weight and multiplying by the body weight. Eg For an average adult, the BMR is about 1,800 kcal for men (70 kg) and 1,300 kcal for women (50 kg). Using the above formula, this 70kg man’s RMR=1680kcal and the 50kg woman is 1200kcal. From 50–70% of the daily energy expenditure in sedentary individuals is attributable to the RMR 9 Dr. Mwale, 2023 6b) DIET-INDUCED THEMOGENESIS/THERMIC EFFECT OF FOOD: After the ingestion of food, our metabolic rate increases because energy is required to digest, absorb, distribute, and store nutrients. This can be observed by the production of heat by the body which increases as much as 30% above the resting level during the digestion and absorption of food. NOTE: The energy required to process the types and quantities of food in the typical American diet is probably equal to approximately 10% of the kilocalories ingested. This amount is roughly equivalent to the error involved in rounding off the caloric content of carbohydrate, fat, and protein to 4, 9, and 4, kcal/g respectively and so thermic effect of food is often ignored and calculations of the daily energy expenditure are based simply on the RMR and the energy required for physical activity. 10 Dr. Mwale, 2023  6c) PHYSICAL ACTIVITY: Physical muscular activity provides the greatest variation in energy expenditure. Therefore the amount of energy consumed depends on the duration and intensity of the physical activity. Estimation of daily expenditure of energy on physical activity can be done by recording the type and duration of all activities A rough estimate of the energy required per day for physical activity can be made by using a value of 30-50% of the RMR (per day) for a very sedentary person (such as a medical student who does little but study) and a value of 60 to 70% of the RMR (per day) for a person who engages in about 2 hours of moderate exercise per day or a value of 100% or more of the RMR for a person who Dr. Mwale, 2023 does several hours of heavy exercise per day 11  7 Acceptable Macronutrient Distribution Range (AMDR) -How many calories from carbohydrates, proteins, lipids are acceptable? 45-65% kcal for carbohydrates 20-35% kcal for lipids 10-35% kcal for proteins -This range prevents chronic diseases How does one know their AMDR? By performing a Nutritional Assessment. -Deficiency or excess overtime leads to malnutrition -under nutrition -over nutrition Similar symptoms include diarrhea, skin rashes, fatigue etc 12 Dr. Mwale, 2023  In the Nutritional Assessment, get 1. History (dietary and health) 2. Anthropometric measurements -aims to achieve healthy body weight WHAT IS THE IDEAL WEIGHT? This is guided by the body mass index (BMI), calculated as weight/height2 (kg/m 2) Adults with BMI values below 18.5 are considered underweight. Those with BMIs between 18.5 and 24.9 are considered to be in the healthy weight range, Those between 25 and 29.9 are in the overweight or pre- obese range Those above 30 are in the obese range. 3. Physical examination -eyes (discoloration/ pale) -tongue -skin 4. Laboratory blood test 13 Dr. Mwale, 2023  14 Dr. Mwale, 2023  6. DIETARY CARBOHYDRATES Classification of Carbohydrates 15 Dr. Mwale, 2023  DIETARY CARBOHYDRATES cont.... No specific carbohydrates have been identified as dietary requirements BUT their role is to provide energy They are not essential nutrients, because the carbon skeletons of most amino acids can be converted into glucose. Absence of dietary carbohydrate leads to ketone body production, and degradation of body protein whose constituent amino acids provide carbon skeletons for gluconeogenesis. The RDA for carbohydrate is set at 130 g/day for adults and children, based on the amount of glucose used by carbohydrate-dependent tissues, such as the brain and erythrocytes. 16 Dr. Mwale, 2023  7. DIETARY FATS Although most lipids required for cell structure, fuel storage, or hormone synthesis can be synthesized from carbohydrates or proteins, we need a minimal level of certain dietary lipids for optimal health-known as essential fatty acids. These are required in our diet because we cannot synthesize fatty acids with these particular arrangements of double bonds. The essential fatty acids α-linoleic and α-linolenic acid are supplied by dietary plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are supplied in fish oils. They are the precursors of the eicosanoids (a set of hormone-like molecules that are secreted by cells in small quantities and have numerous important effects on neighboring cells). The eicosanoids include the prostaglandins, thromboxanes, leukotrienes, and other related compounds. Dr. Mwale, 2023  DIETARY FATS cont… A. Plasma Lipids Plasma cholesterol may arise from the diet (animal products) or from endogenous biosynthesis and in either case, cholesterol is transported between the tissues in combination with protein and phospholipids as lipoproteins. B. Classes of Lipoproteins 1. Low-density lipoprotein (LDL) 2. high-density lipoprotein (HDL): The level of plasma cholesterol is not precisely regulated, but rather varies in response to the diet and so elevated levels of LDL result in an increased risk for Coronary Heart Disease (CHD). This risk increases progressively with higher values for serum total cholesterol and a much stronger correlation exists between the levels of blood LDL cholesterol and heart disease. Note that high levels of HDL cholesterol have been associated with a decreased risk for heart disease. Dr. Mwale, 2023  DIETARY FATS cont… C. Dietary Fats-Triacyglycerols are quantitatively the most important class of dietary fats where their influence on blood lipids is determined by the chemical nature of their constituent fatty acids ie saturated , monosaturated, polysaturated fats and trans- fatty acids. 1. SATURATED FATS These are triacylglycerols composed primarily of fatty acids whose hydrocarbon chains do not contain any double bonds. Saturated fatty acids with carbon chain lengths of 14 (myristic) and 16 (palmitic) are most potent in increasing the serum cholesterol. Stearic acid (18 carbons—found in many foods including chocolate) has little effect on blood cholesterol. Consumption of saturated fats is positively associated with high levels of total plasma cholesterol and LDL cholesterol, and an increased risk of CHD. Other sources include are dairy and meat products and some vegetable oils, such as coconut and palm oils. Dr. Mwale, 2023  DIETARY FATS cont… 2. Monounsaturated fats Triacylglycerols containing primarily fatty acids with one double bond Source include vegetables and fish. When substituted for saturated fatty acids in the diet, monounsaturated fats lower both total plasma cholesterol and LDL cholesterol, but maintain or increase HDL cholesterol. 3. Polyunsaturated fats Contain primarily fatty acids with more than one double bond The effects of polyunsaturated fatty acids (PUFAs) on cardiovascular disease is influenced by the location of the double bonds within the molecule. Dr. Mwale, 2023  Polyunsaturated fats cont… a) ω-6 Fatty acids The location of the first double bond beginning at the sixth bond position when starting from the methyl end of the fatty acid molecule are referred to as ω-6 Fatty acids Consumption of fats containing these long-chain ω-6 PUFAs, principally linoleic acid, 18:2(9,12), obtained from vegetable oils, lowers plasma cholesterol when substituted for saturated fats. Plasma LDL are lowered, but HDL, which protect against CHD, are also lowered. Dr. Mwale, 2023  Polyunsaturated fats cont… b) ω-3 Fatty acids These are long-chain, PUFAs, with the first double bond beginning at the third bond position from the methyl end. Dietary ω-3 polyunsaturated fats suppress cardiac arrhythmias, reduce serum triacylglycerols, decrease the tendency for thrombosis, lower blood pressure, and substantially reduce risk of cardiovascular mortality, However, they have little effect on LDL or HDL cholesterol levels. Dr. Mwale, 2023  4. Trans fatty acids These are chemically classified as unsaturated fatty acids, but behave more like saturated fatty acids in the body, that is, they elevate serum LDL (but not HDL), and they increase the risk of CHD. They do not occur naturally in plants, but occur in small amounts in animals. They are formed during the hydrogenation of liquid vegetable oils, for example, in the manufacture of margarine and partially hydrogenated vegetable oil. Dr. Mwale, 2023  SUMMARY OF THE ESSENTIAL FATTY ACIDS TYPE OF FAT METABOLIC EFFECTS EFFECTS ON DISEASE PREVENTION Saturated Increases LDL Little effect on Increased incidence of HDL CHD; may increase risk of prostate and colon cancer Monounsaturated Lowers LDL Lowers HDL Reduced incidence of CHD Polysaturated ω-6 Lowers LDL Lowers HDL Reduced incidence of CHD Provide arachidonic acid, an important precursor of prostaglandins and leukotrienes Polysaturated ω-3 Little effect on Little effect on Reduced incidence of CHD LDL HDL Reduced risk of sudden Supresses cardiac arrhythmias, cardiac death reduce serum triacyglycerols, decrease the tendency for thrombosis, lower blood pressure Trans Increases LDL Lowers HDL Increased incidence of CHD  8. DIETARY PROTEIN High quality of a dietary protein contain all the essential amino acids required for tissue maintenance. Nine of the 20 amino acids needed for the synthesis of body proteins are essential—that is, they cannot be synthesized in humans and so must be obtained from the diet. A. 9 ESSENTIAL AMINO ACIDS These are lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine, and histidine. Certain amino acids are conditionally essential, that is, required in the diet only under certain conditions. For example: -Children and pregnant women have a high rate of protein synthesis to support growth, require some arginine from the diet, although it can be synthesized in the body. -Histidine is essential in the diet of the adult in very small quantities because adults efficiently recycle histidine. Dr. Mwale, 2023  CONDITIONALLY ESSENTIAL AMINO ACIDS cont… -Tyrosine is considered conditionally essential. It is synthesized from phenylalanine, and it is required in the diet if phenylalanine intake is inadequate, or if an individual is congenitally deficient in an enzyme required to convert phenylalanine to tyrosine (the congenital disease phenylketonuria). -Cysteine is also considered as conditionally essential. It is synthesized by using sulfur from methionine, and it also may be required in the diet under certain conditions. Dr. Mwale, 2023  B. ANIMAL SOURCES OF PROTEIN These include meat, poultry, milk, and fish They have a high quality because they contain all the essential amino acids in proportions similar to those required for synthesis of human tissue proteins. C. PLANT SOURCES OF PROTEIN These include wheat, corn, rice, and beans They have a lower quality than do animal proteins. However, proteins from different plant sources may be combined in such a way that the result is equivalent in nutritional value to animal protein. For example, wheat which is lysine-deficient but methionine-rich, may be combined with kidney beans which is methionine-poor but lysine-rich, to produce an improved biologic value. Dr. Mwale, 2023  9. NITROGEN BALANCE This occurs when the amount of nitrogen consumed equals that of the nitrogen excreted in the urine, sweat, faeces and other excretions. Most healthy adults are normally in nitrogen balance. 1. Positive nitrogen balance This occurs when nitrogen intake exceeds nitrogen excretion. It is observed during situations in which tissue growth occurs, for example, in childhood, pregnancy, or during recovery from an emaciating illness. Consumption of excess protein has no physiologic advantage and so protein consumed in excess of the body’s needs is deaminated, and the resulting carbon skeletons are metabolized to provide energy or acetyl coenzyme A for fatty acid synthesis. Dr. Mwale, 2023  2. Negative nitrogen balance This occurs when nitrogen loss is greater than nitrogen intake. It is associated with inadequate intake of dietary protein, lack of an essential amino acid, or during physiologic stresses, such as trauma, burns, illness, or surgery. If a negative nitrogen balance persists for too long, bodily function will be impaired by the net loss of critical proteins. 3. NOTE THE PROTEIN-SPARING EFFECT OF CARBOHYDRATE: The dietary protein requirement is influenced by the carbohydrate content of the diet. When the intake of carbohydrates is low, amino acids are deaminated to provide carbon skeletons for the synthesis of glucose that is needed as a fuel by the central nervous system. If carbohydrate intake is less than 130 g/day, substantial amounts of protein are metabolized to provide precursors for gluconeogenesis. Therefore, carbohydrate is considered to be “protein-sparing,” because it allows amino acids to be used for repair and maintenance of tissue protein rather than for gluconeogenesis. Dr. Mwale, 2023  4. FUEL STORES. Any dietary fuel that exceeds the body’s immediate energy needs is stored, mainly as triacylglycerol (fat) in adipose tissue, as glycogen (a carbohydrate) in muscle, liver, and other cells, and, to some extent, as protein in muscle. When we are fasting, between meals and overnight while we sleep, fuel is drawn from these stores and is oxidized to provide energy. Dr. Mwale, 2023 Dr. Mwale, 2023  VITAMINS 32 Dr. Mwale, 2023  VITAMINS - Vitamins are organic nutrients/molecules that are required in small quantities in the diet and serve specialized functions in the body eg normal growth, maintenance and reproduction.. - They may either not be synthesized at all by the human body or may be synthesized only at a rate not consistent with normal health - They do not undergo degradation to provide energy - Two forms of vitamins: fat-soluble & water-soluble - Most of the water soluble vitamins are nearly always precursors of coenzymes; have more functional groups that interact with water BUT fat soluble vitamins are more often encountered as physiological regulators and antioxidants; have complex hydrocarbon structures with a few of these having functional groups 33 Dr. Mwale, 2023  VITAMINS cont…. Water-soluble vitamins are readily absorbed in the intestine; excess vitamins are eliminated in urine and sweat BUT absorption of fat-soluble vitamins depends on mixed bile salt micelles; excess vitamins are stored in the liver and thus are not be eliminated from the body. Fat-soluble vitamins deficiencies are most likely in patients with fat mal-absorption. Fat-soluble vitamins supplements are most effective when taken with a fatty meal Water-soluble vitamins are transported in blood Fat-soluble vitamins are transported either as constituents of lipoproteins or bound to specific plasma proteins 34 Dr. Mwale, 2023  ASSIGNMENT 1 TO BE HANDED IN DURING YOUR TEST/EXAM Draw a table giving ALL the differences between water and fat soluble vitamins. Water-Soluble Vitamins Fat-Soluble Vitamins 1.Are water soluble 1.Are fat soluble 2………… 2……… 3…….. 3……… 35 Dr. Mwale, 2023  Fat-soluble Vitamins 1. Vitamin A Active forms are retinol, retinal, retinoic acid; found in abundance in foods of animal origin such as dairy products, fish and liver. Some foods of plant origin contain the antioxidant, β- carotene (4th form), which the body oxidatively cleaves in the intestine and is converted to vitamin A (retinal). A) Retinal is the aldehyde derived from the oxidation of retinol (so easily undergo retinal to retinol interconvesion) It is pigment that produces a neural signal to the brain by initiating the response of rod and cone cells of the retina to light. How? 36 Dr. Mwale, 2023  Fat-soluble Vitamins 1. Vitamin A Active forms are retinol, retinal, retinoic acid; found in abundance in foods of animal origin such as dairy products, fish and liver. Some foods of plant origin contain the antioxidant, β- carotene (4th form), which the body oxidatively cleaves in the intestine and is converted to vitamin A (retinal). A) Retinal is the aldehyde derived from the oxidation of retinol (so easily undergo retinal to retinol interconvesion) It is pigment that produces a neural signal to the brain by initiating the response of rod and cone cells of the retina to light. How? 37 Dr. Mwale, 2023  Retinal cont…. Rhodopsin, the visual pigment of the rod cells in the retina,has 11-cis retinal specifically bound to the protein opsin and so when rhodopsin is exposed to light, a series of photochemical isomerizations occurs, resulting in the release of all-trans retinal and opsin. This process triggers a nerve impulse that is transmitted by the optic nerve to the brain which processes the impulse into an image. Regeneration of rhodopsin requires isomerization of all-trans retinal back to 11-cis retinal, which combines with opsin to form rhodopsin, thus completing the cycle. Similar reactions are responsible for color vision in the cone cells. Note that retinal is also essential for normal reproduction, ie supporting spermatogenesis in the male and preventing fetal resorption in the female. 38 Dr. Mwale, 2023  Vitamin A cont… B) Retinoic acid is derived from the oxidation of retinol. It cannot be reduced in the body, and, therefore, cannot give rise to either retinal or retinol. It binds to nuclear receptors involved in the regulation of cell growth and differentiation. It also promotes the development of epithelial tissue including skin. It is required for the synthesis of the iron transport protein transferrin. NOTE: Retinoic acid is inactive in maintaining reproduction and in the visual cycle, although as already mentioned, promotes growth and differentiation of epithelial cells So animals given vitamin A only as retinoic acid from birth are blind and sterile 39 Dr. Mwale, 2023  Fat-soluble Vitamins C) Retinol is important for the synthesis of glycoproteins and mucopolysaccharides. It is found in animal tissues as a retinyl ester with long-chain fatty acids Also needed for normal growth and for mucus secretions and so reason why the skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Also required for the synthesis of the transferrin and for normal reproduction, ie supporting spermatogenesis in the male and preventing fetal resorption in the female. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers (and some other aspects of immunity as well). 40 Dr. Mwale, 2023  Absorption and transport of vitamin A to the liver Retinyl esters present in the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids. Retinol derived from esters and from the cleavage and reduction of carotenes is re-esterified to long-chain fatty acids in the intestinal mucosa and secreted as a component of chylomicrons into the lymphatic system. Retinyl esters contained in chylomicron remnants are taken up by, and stored in, the liver. Release of Vitamin A from the liver When needed, retinol is released from the liver and transported to extrahepatic tissues by the plasma retinol-binding protein (RBP). The retinol–RBP complex attaches to specific receptors on the surface of the cells of peripheral tissues, permitting retinol to enter. 41 Dr. Mwale, 2023  Mechanism of action of vitamin A Retinol is oxidized to retinoic acid which binds with high affinity to specific receptor proteins present in the nucleus of target tissues, such as epithelial cells. This activated retinoic acid–receptor complex interacts with nuclear chromatin to regulate gene expression, resulting in control of the production of specific proteins that mediate several physiologic functions such as retinoids controlling the expression of the gene for keratin in most epithelial tissues of the body. 42 Dr. Mwale, 2023  Fat-soluble Vitamins cont.. DEFICIENCY OF VITAMIN A Night blindness –this involves both time taken to adapt to darkness and the ability to see in poor light. Severe deficency leads to xerophthalmia (progressive keratinization of the cornea) including pathologic dryness of the conjunctiva and cornea as Vitamin A is required for the differentiation and proliferation of the epithelium of the conjunctiva and cornea. When untreated, xerophthalmia results in corneal ulceration and, ultimately, in blindness because of the formation of opaque scar tissue. Infection usually sets in causing hemorrhaging of the eyes and permanent loss of vision. Very dry, rough skin may indicate a lack of vitamin A, since retinol and/or retinoic acid down regulate the synthesis of keratin, *Excess keratin leads to rough surface in place of moist and pliable epithelium. 43 Dr. Mwale, 2023  DEFICIENCY OF VITAMIN A cont… Keratomalacia This is severe eye disorder as a result of vitamin A deficiency. In this condition, normal epithelium is replaced by inappropriately keratinised epithelium leading to opaque cornea. Acne and psoriasis Dermatologic problems such as acne and psoriasis can be effectively treated with retinoic acid or its derivatives. 44 Dr. Mwale, 2023  Fat-soluble Vitamins DEFICIENCY OF VITAMIN A cont…. Other signs of deficiency include decreased resistance to infections, due to keratinization of mucosal lining in the respiratory, gastroinstestinal and genitourinary tracts. Fissures which develop in the mucosal lining may allow microorganisms to enter. Vitamin A deficiency can also cause iron deficiency-like anemia, even in the presence of adequate iron. VITAMIN A TOXICITY-referred to as Hypervitaminosis A. This is due to excess (exceeding 7.5 mg/day) intake of vitamin A Symptoms of vitamin A toxicity include dry, itchy skin, bone pain, nausea, enlarged liver and spleen and loss of appetite. Signs of severe overuse over a short period of time include dizziness, blurred vision and slow growth. Other signs may be seen in the nervous system, where a rise in intracranial pressure may mimic the symptoms of a brain tumor. Pregnant women particularly should not ingest excessive quantities of vitamin A because of its potential for causing congenital malformations in the developing fetus. 45 Dr. Mwale, 2023  Xerophthalmia 46 Dr. Mwale, 2023  Fat-soluble Vitamins cont………. 2. Vitamin D Involved in homeostasis Found in animals (as cholecalciferol-vitamin D3), oily fish(e.g., herring, salmon,sardines), in cod liver oil, milk and other diary products Found in plants (ie Ergocalciferol-vitamin D2), Effect in man: i)increases Ca absorption from intestines How? Calcitriol (formed from the hydroxlation of Cholecalciferol) binds to a cytosolic receptor. The calcitriol–receptor complex then moves to the nucleus where it selectively interacts with the cellular DNA resulting into enhanced calcium uptake by an increased synthesis of a specific calcium-binding protein. ii)causes Ca mobilization from bone iii)reduces excretion of calcium (by stimulating resorption in the distal renal) iv) increases phosphate excretion by kidneys Note that sunlight converts 7-dehydrocholesterol to a form of vitamin D, cholecalciferol, in the skin and therefore not strictly a vitamin but an endogenous vitamin precursor. 47 Dr. Mwale, 2023  Fat-soluble Vitamins cont………. 2. Vitamin D cont…… v)Vitamin D is also involved in insulin secretion, synthesis and secretion of parathyroid and thyroid hormones (via interaction with intracellular receptor proteins), modulation of cell proliferation (ie interacts with DNA in the nucleus of target cells in a manner similar to that of vitamin A, and either selectively stimulates gene expression or specifically represses gene transcription), normal functioning of immune system, regulation of blood pressure and normal neuromuscular function. DEFICIENCY OF VITAMIN D In growing children, deficiency include rickets (soft and pliable bones) due to improper mineralization of osteoid matrix and cartilage. Symptoms of rickets include delayed growth, pain in the spine, pelvis and legs and muscle weakness. Because rickets softens the growth plates at the ends of a child’s bones, it can cause skeletal deformities such as bowed legs, abnormally curved spine, thickened wrists and ankles and breast bone projection. 48 Dr. Mwale, 2023  Fat-soluble Vitamins cont………. DEFICIENCY OF VITAMIN D cont….. Vitamin D deficiency in adults may result in osteomalacia caused by demineralization of preexisting bones causing it to become softer and increased susceptibility to fracture. Insufficient exposure to daylight and/or deficiencies in vitamin D consumption occur predominantly in infants and the elderly. Renal osteodystrophy is chronic renal failure that results from the decreased ability to form the active form of vitamin D Supplementation with calcitriol is an effective therapy for these conditions. VITAMIN D TOXICITY Signs of vitamin D toxicity(excess of 100,000 IU for weeks or months) include excess calcium in the blood, contraction of blood vessels, high blood pressure, and calcinosis (calcification of soft tissues). Toxicity can also lead to hypercalcemia leading to hypercalciuria resulting in formation of renal stones 49 Dr. Mwale, 2023  RICKETS Osteomalacia 50 Dr. Mwale, 2023  Fat-soluble Vitamins cont……. 2. Vitamin E 3 forms exist:α-, β-, γ- tocopherol/tocotrienols; most active is the α-form Vitamin E benefits the body by acting as an antioxidant, in cell membranes and plasma lipoproteins. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids. They also prevent the oxidation of LDL, which maybe important in reducing the risk of cardiovascular diseases since the oxidized form of LDL is atherogenic. Source of vitamin E in the diet comes from vegetable oil (soybean, corn, cottonseed, and safflower), fruits and vegetables, grains, nuts (almonds and hazelnuts), seeds (sunflower) and fortified cereals. In rats, it is known to act as an anti-sterility vitamin. 51 Dr. Mwale, 2023  Fat-soluble Vitamins cont……. 2. Vitamin E cont…. VITAMIN E DEFICIENCY Though rare it can only occur in premature infants and in those unable to absorb or transport fats. It causes fragile red blood cells and the appearance of abnormal cellular membranes. VITAMIN E TOXICITY Vitamin E can act as an anticoagulant and may increase the risk of bleeding problems. Occasionally, muscle weakness, fatigue, nausea, and diarrhea have been reported to occur. However, Vitamin E is the least toxic of the fat-soluble vitamins even at doses of 300 mg/day 52 Dr. Mwale, 2023  2. Vitamin K 2 forms exist:K1 & K2 derived from menadione Vitamin K2 is naturally produced by intestinal bacteria, and plays an essential role in normal blood clotting (prothrombin biosynthesis) It is also required for the carboxylation of glutamate residues (formation of γ-carboxyglutamate,Gla) in calcium-binding bone proteins which is required for normal bone mineralization. How? As stated, Vit. K–dependent carboxylation of glutamic acid residues is central to synthesis of prothrombin and blood clotting factors II, VII, IX, and X inactive precursor molecules which forms a mature clotting factor that is capable of subsequent activation. Note that the carboxylation is sensitive to inhibition by dicumarol, an anti- coagulant and by warfarin, a synthetic analog of vitamin K. There is also an interaction of prothrombin with platelets, where the Gla residues of prothrombin bind to calcium ions (prothrombin–calcium complex) which is then able to bind to phospholipids that are essential for blood clotting on the surface of platelets. 53 Dr. Mwale, 2023  Vitamin K cont… Sources of vitamin K are green, leafy-vegetables (spinach, cauliflower, cabbage and broccoli), and certain vegetables oils (including soybean oil, canola oil and olive oil). Animal foods, in general, contain limited amounts of vitamin K. Vit.K1 available in green leaves of plants as phylloquinone 54 Dr. Mwale, 2023  VITAMIN K DEFICIENCY Most easily detectable symptom of vitamin K deficiency is increased coagulation time. Deficiency is most commonly seen in newborn babies lacking the intestinal bacteria to produce vitamin K. Because human milk provides only about one fifth of the daily requirement for vitamin K, it is recommended that all newborns receive a single intramuscular dose of vitamin K as prophylaxis against hemorrhagic disease. People taking antibiotics may lack vitamin K temporarily (hypoprothrombinemia) because intestinal bacteria are sometimes killed as a result of long-term use of antibiotics VITAMIN K TOXICITY Excessive amounts can cause the breakdown of red blood cells (hemolytic anemia and jaundice in infants.) and liver damage Prolonged administration of large doses of synthetic vitamin K (menadione) is no longer used to treat vitamin K deficiency therefore soprotection.com 55 Dr. Mwale, 2023