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