the fat-soluble vitamins dr k n prasad md., dnb. community medicine
TRANSCRIPT
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The Fat-Soluble Vitamins
Dr K N Prasad MD., DNB.
Community Medicine
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Vitamin DeficienciesIt takes months to years for fat soluble
vitamin deficiencies to develop because of relatively large stores
Result of• Decreased intake• Decreased absorption• Increased utilization• Increased loss
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Functions of Vitamin A • Vision
– Phototransduction
• Regulation of gene expression • Immunity
– Maintenance of the integrity of skin, and mucosal cells (airways, digestive and urinary tract)
– Differentiation of WBC, activation of T-lymphocytes
• Growth and development • Red blood cell production
– Stem cells differentiation into red blood cells – Mobilization of iron from storage sites
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Dietary Sources of Vitamin A• Animal foods: Liver, fish oil, kidney, egg yolk,
butter• Plants: Carrots, dark green leafy vegetables (beta-
carotene), spinach, broccoli, sweet potatoes• RDA: 700-900 mcg
1mcg of retinol=3.33 IU of vit. A
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Vitamin A Deficiency• Ancient Egyptians recognized that night blindness
could be treated by consumption of liver
• 3rd most common nutritional deficiency in the world
• Night blindness, complete blindness, and xerophthalmia common in malnourished children in Asia, Africa, and South America
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Causes of Vitamin A Deficiency
• Inadequate intake (strict vegetarian diet)
• Fat malabsorption– Crohn's ileitis– Pancreatic insufficiency – Cystic fibrosis– Cholestatic liver disease
• Severely limited protein intake – Vit. A carried by RBP
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Vitamin A Deficiency Clinical Manifestations
1. Night blindness
2. Bitot's spots - Abnormal squamous cell proliferation and keratinization of the conjunctiva
Xerophtalmia3. Irreversible eye conditions:
XerosisCorneal perforationKeratomalaciaPunctate keratopathy
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Vitamin A Deficiency• Dermatologic manifestations:
– Follicular hyperkeratosis(Dry, rough, scaly skin)
– Destruction of hair follicles
• Impairment of the humoral and cell mediated immune response– direct and indirect effects on phagocytes / T cells:
incidence of respiratory disease/diarrhea rate of mortality from infections in children
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Assessment of Vitamin A Status
• Clinical :• Biochemical:
– Deficiency: serum vit. A level <0.35mcmol/L (<10mcg/dl) measured by HPLC
– 50% increase in RDR assay - change in serum retinol level before and 5 hrs after oral dose of 450-1000 mcg of retinyl ester
• Histologic (conjunctival impression cytology)• Physiologic (measurement of dark adaptation)• Dietary
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Supplementation of Vitamin A• Tolerable upper level for adult: 10,000 IU/d (3
mg/d)
• Retinol intake of 5,000 IU/day have been associated with risk of osteoporosis in older adults
• Rx of Vit. A deficiency: 30 mg of retinol palmitate, single IM injection (children)
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Vitamin D
• Vitamin D and its metabolites play an important role in calcium homeostasis and bone metabolism
• Vitamin D deficiency (referred to "rickets“) was first described in the mid 1600s by Whistler and Glisson
• Severe bone-deforming disease: enlargement of epiphyses of long bones, bowing of the legs, bending of the spine and toneless muscles
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Functions of Vitamin D • Calcium homeostasis
• Immune response IL4 production, T cell activity
• Cell growth and differentiation
• Apoptosis – Protects against peroxidation
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Sources of Vitamin D • Vitamin D is found naturally in very few foods• Dietary source: fatty fish (mackerel, salmon,
sardines), cod-liver oil, eggs yolks• Fortified milk (vitamin D2/D3), cereals and bread
products, orange juice• Infant formula is fortified with vit. D (400 IU per
quart)
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Risk Factors for Vitamin D Deficiency
• Exclusively breast fed infants - human milk 25 IU/L of vit. D
• Dark skin - vit. D synthesis with exposure to sunlight
• Fat malabsorption - absorption of vit. D• Elderly - synthesis of vit. D in the skin +
stay indoors• Institutionalized adults• Obesity - vit. D deposited in body fat stores
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Findings in Vitamin D Deficiency intestinal absorption of calcium and phosphorus
– Hypocalcemia– Hypophosphatemia – Phosphaturia – Secondary hyperparathyroidism (bone resorption)
– Demineralization of bones• Osteoporosis/ostoemalacia in adults• Rickets in children
– Muscle pain/weakness
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Vitamin D Deficiency Children
Rickets• Failure of bone mineralization in infants
and children – Delayed closure of the fontanels (soft spots)
in the skull
– Deformed rib cage in infants
• Seizures from hypocalcemia
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Vitamin D Supplements• RDI: 400 IU (0.01 mg of vit. D3)
• Multivitamin supplements with vit. D – Children 200 IU (5 mcg)
– Adults 400 IU (10 mcg)
• Vitamin D (D3) supplement: 400-1,000 IU
• Older adults (>65 years) + those with minimal sun exposure should take 800 IU/d of vit. D
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Treatment of Vitamin D Deficiency
• Osteomalacia: – Vit D3 orally: 4,000-8,000 IU/d (0.1-0.2 mg)
– If malabsorption up to 50,000 IU/d orally
• Monitor 25-OH-vit. D levels q 3-4 weeks until normal
• Sun exposure: 10-15 minutes of on the arms and legs at least x3 weekly
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Functions of Vitamin E • A free radical scavenger, protects PUFA (a
structural component of the cell membranes) from peroxidation
• Inhibits activity of protein kinase C• Affects the expression and activity of immune
and inflammatory cells• Inhibits platelet aggregation and enhances
vasodilation
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Vitamin E • Food source: vegetable oils (olive, sunflower,
safflower), nuts and seeds, whole grains, green leafy vegetables
• Vit. E is destroyed by heat
• The RDA for vitamin E– Women 8 mg/d – Men 10 mg/d
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Vitamin E Deficiency
• Vitamin E deficiency is uncommon due to the abundance of tocopherols in our diet
• Divided to:– Subclinical (low serum tocopherol level)– Clinically evident
• Consequences of vit. E deficiency – Neuromuscular disorders– Hemolysis
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Symptoms of Vitamin E DeficiencyNeurological:
– Spinocerebellar ataxia – Peripheral neuropathy– Muscle weakness/skeletal myopathy– Pigmented retinopathy (retinitis pigmentosa)
• Hematologic: – Hemolysis- red blood cell life span– Hemolytic anemia common with vitamin E
deficiency in premature infants
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Vitamin E Supplementation• Tolerable upper intake: 1,500 IU/d (1,000 mg/d)
• Side effects: impaired blood clotting/ risk of hemorrhage seen in adults with vit. E < 2,000 mg/d
• Large oral supplements of vit. E have been associated with– Necrotizing enterocolitis in infants– Higher mortality due to hemorrhagic strokes in adults
• Impaired absorption of vitamins A and K seen with large vitamin E supplements in animals
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Vitamin K • The "K" is derived from the German word "koagulation“
• Two forms of vitamin K– Vitamin K1 (phylloquinone) - dietary from plants– Vitamin K2 (menaquinone) - synthesized by gut
micro-flora
• Vitamin K is essential for the functioning of several proteins involved in blood clotting
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Functions of Vitamin K• A major role in coagulation pathways
• Essential for activity of carboxylase enzymes
responsible for carboxylation of glutamate to gamma-carboxyglutamate (liver) – Clotting factors – prothrombin, factors VII, IX, X
– Anticoagulant proteins C, S
– Osteocalcin
• Hydroxylation of osteocalcin (bone matrix)
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Vitamin K
• Dietary source – Liver– Oils (soy, canola, olive)– Green leafy vegetables (spinach, broccoli)
• Requirement of vitamin K: 65-80 mcg/d
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Signs and Symptoms of Vitamin K Deficiency
• Mucosal bleeding
• Easy bruisability
• Splinter hemorrhages
• Melena
• Hematuria
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Vitamin K• Treatment of coagulopathy
– Vitamin K in doses 1-25 mg orally, IM, IV, SC
• Vitamin K IV can cause severe anaphylactic-type reaction
• Prevention of hemorrhagic disease of the newborn– Vitamin K 0.5-1 mg IM at birth
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The Water-Soluble Vitamins
Dr K N Prasad MD., DNB.
Community Medicine
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Overview of Water-Soluble Vitamins
• Dissolve in water
• Subject to cooking losses
• Function as a coenzyme
• Participate in energy metabolism
• 50-90% of B vitamins are absorbed
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Thiamin
• Food Sources : Wide variety of food
• White bread, cereal• Enriched grains/
whole grains• Thiaminase found in
raw fish
• Absorption, Transport, Metabolism:
• Absorbed in the jejunum by a carrier-mediated system
• Transported by RBC in the blood
• Excess quickly excreted in the urine
Contains sulfur and nitrogen groupDestroyed by alkaline and heatCoenzyme: Thiamin pyrophosphate (TPP)
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RDA For Thiamin
• 1.1 mg/day for women• 1.2 mg/day for men• Most exceed RDA in diet• Surplus is rapidly lost in urine; non toxic
• Risk For Deficiency?• Poor• Alcoholics• Elderly• Diet consisting of highly processed foods
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Deficiency of Thiamin
• Occurs where rice is the only staple
• Dry beriberi–Weakness, nerve degeneration, irritability,
poor arm/leg coordination, loss of nerve transmission
• Wet beriberi–Edema, enlarge heart, heart failure
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Riboflavin• Coenzymes:
– Flavin mononucleotide (FMN)
– Flavin adenine dinucleotide (FAD)
• Oxidation-reduction reactions
• Electron transport chain
• Citric Acid Cycle
• Catabolism of fatty acids
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Food Sources of Riboflavin
• Milk/products, Enriched grains
• Liver, Oyster, Brewer’s yeast
• Sensitive to uv radiation (sunlight)• Daily requirement :• 1.1 mg/day for women• 1.3 mg/day for men• Average intake is above RDA• Toxicity not documented
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• Deficiency of Riboflavin • Ariboflavinosis
– Glossitis, cheilosis, seborrheic dermatitis, stomatitis, eye disorder, throat disorder, nervous system disorder
• Occurs within 2 months • Usually in combination with other deficiencies
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Niacin• Nicotinic acid (niacin) & nicotinamide (niacinamide)• Coenzyme
– Nicotinamide adenine dinucleotide (NAD)– Nicotinamide adenine dinucleotide phosphate (NADP)
• Oxidation-reduction reaction• Metabolic reactions
• Heat stable; little cooking loss
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Sources of Niacin
• Mushrooms
• Enriched grains
• Beef, chicken, turkey, fish
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RDA for Niacin• 14 mg/day for women
• 16 mg/day for men
• Deficiency • Pellagra -3 Ds
– Occurs in 50-60 days– Decrease appetite & weight
• Prevented with an adequate protein diet• Who is at risk?
– (Untreated) corn as main staple, poor diet, Hartnup disease, alcoholics
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Vitamin B-6: Pyridoxal, Pyridoxine, Pyridoxamine
• Main coenzyme form: pyridoxal phosphate (PLP)
• Activate enzymes needed for metabolism of CHO, fat , protein
• Synthesis of hemoglobin and oxygen binding and white blood cells
• Synthesis of neurotransmitters
• Food sources:• Meat, fish, Poultry, Whole grains, Banana, Spinach, Potato
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RDA for Vitamin B-6
• 1.3 mg/day for adults
• 1.7 mg/day for men over 50
• 1.5 mg/day for women over 50
• Daily Value set at 2 mg
• Average intake is more than the RDA
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Deficiency of Vitamin B-6
• Microcytic hypochromic anemia• Seborrheic dermatitis• Convulsion, depression, confusion• Reduce immune response• Peripheral nerve damage
• Requirement: • 1.3 mg/day for adults
• 1.7 mg/day for men over 50
• 1.5 mg/day for women over 50
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Folate (Folic acid, Folacin)
• Consists of pteridine group, para-aminobenzoic acid (PABA), and glutamic acid
• Coenzyme form: tetrahydorfolic acid (THFA)
• Sources:• Fortified breakfast cereals
• Grains, legumes
• Foliage vegetables
• Susceptible to heat, oxidation, ultraviolet light
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Functions of Folate• DNA synthesis
– Transfer of single carbon units
– Synthesis of adenine and guanine
– Anticancer drug methotrexate
• Homocysteine metabolism
• Neurotransmitter formation
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Deficiency of Folate• Similar signs and symptoms of vitamin B-12
deficiency• Pregnant women• Alcoholics
– Interferes with the enterohepatic circulation of bile/folate
• Requirement • 400 ug/day for adults
• Daily Value is set at 400 ug
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Toxicity of Folate
• Epilepsy
• Skin, respiratory disorder
• FDA limits nonprescription supplements to 400 ug per tablet for non-pregnant adults
• OTC Prenatal supplement contains 500 ug
• Excess can mask vitamin B-12 deficiency
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Vitamin B-12• Cyanocobalamin. methylcobalamin,
5-deoxyadenosylcobalamin
• Contains cobalt
• Folate metabolism
• Maintenance of the myelin sheaths
Food Sources: Synthesized by bacteria, fungi and algae, Animal products ,Organ meat. Seafood, Eggs, Milk
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Deficiency of Vitamin B-12• Pernicious anemia
– Never degeneration, weakness– Tingling/numbness in the extremities (parasthesia)– Paralysis and death– Looks like folate deficiency
• Usually due to decreased absorption ability• Achlorhydria especially in elderly• Takes ~20 years on a deficient diet to see nerve
destruction
•Requirement :•2.4 ug/ day for adults and elderly adults
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Vitamin C• Ascorbic acid (reduced form), dehydroascorbic
acid (oxidized form)
• Functions:• Reducing agent (antioxidant)• Iron absorption• Synthesis of carnitine, tryptophan to serotonin, thyroxine,
cortiscosteroids, aldosterone, cholesterol to bile acids• Immune functions• Collagen synthesis
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Food Sources of Vitamin C• Citrus fruits, Potatoes, Cauliflower, Broccoli,• Strawberries, Spinach
• Easily lost through cooking• Sensitive to heat• Sensitive to iron, copper, oxygen
•Requirement:•90 mg/day for male adults•75 mg/day for female adults•+35 mg/day for smokers•Average intake ~72 mg/day
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Deficiency of Vitamin C• Scurvy
– Deficient for 20-40 days – Fatigue, pinpoint hemorrhages– Bleeding gums and joints. Hemorrhages– Associated with poverty
• Rebound scurvy– immediate halt to excess vitamin C supplements
• Who is at risk?– Infants, elderly men
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Pantothenic Acid• Part of Coenzyme-A• Essential for metabolism of CHO,
fat, protein• Food sources:
•Meat •Milk•Mushroom•Liver•Peanut•Adequate Intake = 5 mg/day
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Deficiency of Pantothenic Acid
• Rare
• Burning foot syndrome, listlessness, fatigue, headache, sleep disturbance, nausea, abdominal distress
• Alcoholics at risk
• Usually in combination with other deficiencies
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Biotin• Free and bound form• Metabolism of CHO, fat, protein (C skeleton)• DNA synthesis
Food sources:Cauliflower, yolk, liver, peanuts, cheese, Intestinal synthesis of biotin
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Thought for the day
For everything you have missed, you have gained something else, and for everything you gain, you lose something else.
-Ralph Waldo Emerson
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Thank youThank you
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Biotin Needs
• Adequate Intake is 30 ug/day for adults
• This may overestimate the amount needed for adults
• No Upper Limit for biotin
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Antioxidant
• Can donate and accept hydrogen atoms readily
• Water-soluble intracellular and extracellular antioxidant
• Must be constantly enzymatically regenerated
• Needs are higher for smokers
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Functions of Biotin
• Assists in the addition of CO2 to substances• Carboxylation of acetyl-CoA to form malonyl-
CoA for the elongation of a fatty acid chain• Addition of CO2 to pyruvate to yield
oxaloacetate• Breaks down leucine• Allows 3 essential amino acids to be oxidized
for energy