Download Vitamins

The Fat-Soluble
Vitamins
Dr K N Prasad MD., DNB.
Community Medicine
Vitamin Deficiencies
It 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 (betacarotene), 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
Xerophtalmia
3. Irreversible eye conditions:
Xerosis
Corneal perforation
Keratomalacia
Punctate 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 4501000 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
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 Deficiency
Neurological:
– 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 gammacarboxyglutamate (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 anaphylactictype 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 WaterSoluble Vitamins
• Dissolve in water
• Subject to cooking losses
• Function as a coenzyme
• Participate in energy metabolism
• 50-90% of B vitamins are absorbed
Thiamin
Contains sulfur and nitrogen group
Destroyed by alkaline and heat
Coenzyme: Thiamin pyrophosphate (TPP)
• 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 carriermediated system
• Transported by RBC in
the blood
• Excess quickly
excreted in the urine
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 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