The Fat-Soluble Vitamins
Dr K N Prasad MD., DNB.
Community Medicine
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
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
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
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
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
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
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
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
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)
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
Functions of Vitamin D • Calcium homeostasis
• Immune response IL4 production, T cell activity
• Cell growth and differentiation
• Apoptosis – Protects against peroxidation
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)
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
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
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
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
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
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
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
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
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
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
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
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)
Vitamin K
• Dietary source – Liver– Oils (soy, canola, olive)– Green leafy vegetables (spinach, broccoli)
• Requirement of vitamin K: 65-80 mcg/d
Signs and Symptoms of Vitamin K Deficiency
• Mucosal bleeding
• Easy bruisability
• Splinter hemorrhages
• Melena
• Hematuria
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
The Water-Soluble Vitamins
Dr K N Prasad MD., DNB.
Community Medicine
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
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)
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
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
Riboflavin• Coenzymes:
– Flavin mononucleotide (FMN)
– Flavin adenine dinucleotide (FAD)
• Oxidation-reduction reactions
• Electron transport chain
• Citric Acid Cycle
• Catabolism of fatty acids
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
• 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
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
Sources of Niacin
• Mushrooms
• Enriched grains
• Beef, chicken, turkey, fish
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
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
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
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
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
Functions of Folate• DNA synthesis
– Transfer of single carbon units
– Synthesis of adenine and guanine
– Anticancer drug methotrexate
• Homocysteine metabolism
• Neurotransmitter formation
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
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
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
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
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
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
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
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
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
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
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
Thank youThank you
Biotin Needs
• Adequate Intake is 30 ug/day for adults
• This may overestimate the amount needed for adults
• No Upper Limit for biotin
Antioxidant
• Can donate and accept hydrogen atoms readily
• Water-soluble intracellular and extracellular antioxidant
• Must be constantly enzymatically regenerated
• Needs are higher for smokers
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
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