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VITAMINS

Classification
Two major classification according to chemistry:
A. Fat-soluble vitamins
• Includes vitamins A,D,E and K
• Requires emulsification by bile for absorption
B. Water-soluble vitamins
• Includes the B complex of vitamins - thiamine, riboflavin,
niacin, vitamins B6 and B12, biotin, folate and vitamin C.
• Readily excreted in the urine
• Less likely to accumulate to toxic levels than fat-soluble
vitamins
Overview
• Organic molecules required in trace amounts for health,
growth, and reproduction
• The body depends completely on dietary intake of vitamins
except for Vitamin D
• Vitamins (and trace elements) should be obtained from
foods rather than from supplements.
Hypovitaminosis
• Alcoholism (e.g., thiamine)
• Small bowel disease (e.g., folate and the fat-soluble vitamins;
vitamins A, D, E, and K)
• Vegans (vitamin D, cobalamin)
• Elderly (e.g., vitamin D, folate)
• Conditions that result in decreased absorption in liver and in
biliary tract disease (e.g., vitamins A, D, E, and K)
• Ileal disease or resection (e.g., cobalamin).
• Renal disease (e.g., vitamin D)
• Drugs such as methotrexate (e.g., folate)
• Long-term chronic disease such as acquired
immunodeficiency syndrome.
Fat-Soluble Vitamins
1. Vitamin A (Retinol/retinoic acid)
• Sources:
– Natural pre-formed vitamin A only in fat of animal-related foods:
Whole milk, butter, liver, egg yolks, and fatty fish
– Carotenoids are found in deep green, yellow, and orange fruits and
vegetables (broccoli, cantaloupe, sweet potato, carrots, tomatoes,
spinach
• Retinol is essential for vision at low light intensities,
synthesis of active sulfate, and reproduction
– Retinol is oxidized in the rods into retinal which binds with opsin
forming rhodopsin, allowing dim light vision
• Stored in the liver
Fat-Soluble Vitamins
1. Vitamin A (Retinol/retinoic acid)
• Deficiency
– Squamous metaplasia, especially glandular, follicular
hyperkeratosis; xerophthalmia; night blindness
(nyctalopia), reproductive disorders, vulnerability to
infection
• Toxicity
– Acute: can cause drowsiness, headache, vomiting, stupor,
skin peeling, and papilledema.
– Chronic: teratogenic, osteoporosis, hepatotoxicity.
Carotenoids in excess, distinct orange-yellow skin color
(carotenemia)
Fat-Soluble Vitamins
2. Vitamin E (Tocopherol)
• A powerful antioxidant and the primary defense against
potentially harmful oxidations that cause disease and aging,
protecting unsaturated lipids from peroxidation
• Protect erythrocyte membrane from oxidative stress
• Alpha-tocopherol is the predominant isomers in plasma
• Associated with apo-B containing lipoproteins
• Sources
– Vegetable oils, corn, soy, safflower. Whole grains, seeds,
nuts, wheat germ, green leafy vegetables
Fat-Soluble Vitamins
2. Vitamin E (Tocopherol)
• Deficiency
– Spinocerebellar degeneration, ataxia, hemolytic
anemia
– Susceptible patients: those with cystic fibrosis,
abetalipoproteinemia
• Toxicity
– Mild GI distress, nausea, coagulopathies in
patients receiving anticonvulsants
Fat-Soluble Vitamins
3. Vitamin D (Cholecalciferol)
• A group of related metabolites essential in calcium homeostasis
• Ergocalciferol (vitamin D2) occurs in fungi and plants
• Promotes absorption of calcium and phosphorus; mineralization
of bones and teeth
• Sources
– Food: butter, egg yolks, liver, and fatty fish, vitamin D–
fortified milk
– Sunlight exposure converts 7-dehydrocholesterol of the skin
into vitamin D3
• Both vitamins D2 and D3 require two hydroxylations to the
active form. The first is a 25-hydroxylation in the liver, and the
second is a 1-hydroxylation in the kidney.
Fat-Soluble Vitamins
3. Vitamin D (Cholecalciferol)
• Deficiency:
– Rickets in children; osteomalacia (softening of
bones) in adults; hypocalcemia, tetany
• Toxicity
– Hypercalcemia and hypercalciuria, toxicity above
UL of 50 μg. Bone demineralization, constipation,
muscle weakness, renal calculi
Fat-Soluble Vitamins
4. Vitamin K (Phytomenadione)
• Cofactor of procoagulants—hepatic factors II
(prothrombin), VII, and X, proteins C, S
– Gamma-carboxylation of these factors is dependent on
vitamin K. Gamma carboxyl groups are needed to acquire
net negaive charge required to bind calcium
• Synthesized by the intestinal bacteria in jejunum and
ileum which provides 50% of the vitamin K
requirement
• Others sources: Dark green leafy vegetables
Fat-Soluble Vitamins
4. Vitamin K (Phytomenadione)
• Deficiency: Defective clotting, bleeding
disorder
– Causes: ingestion of vitamin K antagonist like
warfarin sodium (Coumadin) or decreased
synthesis of vitamin K by intestinal bacteria
(newborns)
– Prothrombin time (PT) is INCREASED due to
nonfunctional clotting factors
Assays
1. Vitamin A
• Measurement of retinol using HPLC
2. Vitamin E
• Measurement of alpha-tocopherol using HPLC
3. Vitamin D
• Measurement of 1,25-(OH)2D3 or 25-(OH)D3 using
HPLC
4. Vitamin K
• Prothrombin time
Water-Soluble Vitamins
1. Thiamine (Vitamin B1)
• Function: essential cofactor in the decarboxylation of α-
keto acids such as pyruvate in its conversion to acetyl
coenzyme A.
• Deficiency: dry beri-beri (neuromuscular) and wet beri-beri
(cardiac failure), psychosis (Wernicke-Korsakoff syndrome)
– Lesions of the mamillary bodies and the area that abuts
the third ventricle are distinctive findings
• Assay: measurement of RBC transketolase activity afeter
addition of thiamine pyrophosphate
Water-Soluble Vitamins
2. Riboflavin (Vitamin B2)
• Function: forms two coenzymes: flavin mononucleotide and
flavin adenine dinucleotide
• Deficiency: Ariboflavinosis, cracking and swelling of the lips
(cheilosis), cracking and inflammation of the angles of the
mouth (angular stomatitis), deep-red smooth tongue
(glossitis, atrophy), greasy scaling of the cheeks and the areas
behind the ears (seborrheic dermatitis), corneal
vascularization
• Assay: measurement of RBC—glutathione reductase activity
Water-Soluble Vitamins
3. Pyridoxine (Vitamin B6)
• Function: participates in more than 100 transaminations,
decarboxylations, and other reactions, including the initial steps of
porphyrin synthesis, glycogen mobilization, amino acid transsulfuration,
and neurotransmitter synthesis
• Deficiency: Cheilosis, glossitis, dermatitis, peripheral neuropathy,
convulsions, hyperhomocysteinemia, microcytic hypochromic anemia
• Assay:
– Plasma pyridoxal-5′-phosphate, cation exchange HPLC, assay by
fluorometry
– RBC aminotransferases, reflect long-term pyridoxine status; ALT more
sensitive to B6 deficiency than AST
– urinary 4-pyridoxic acid and xanthurenic acid
Water-Soluble Vitamins
4. Niacin (Nicotinic acid)
• Function: formation of nicotinamide adenine dinucleotide
and its phosphate, which are important in intermediary
metabolism and in a large number of oxidation–reduction
reactions
• Deficiency: Pellagra: Dementia, dermatitis, diarrhea
– prevalent in areas where corn (maize) is the staple food,
as in certain parts of Africa
• Assay: Ratio of NAD and NADP nucleotide (<1)
Water-Soluble Vitamins
5. Folate
• Function: transfer and use one-carbon units in DNA and amino
acid synthesis
• It is widely available from plants and, to a lesser extent, organ
meats
• Deficiency: Megaloblastic anemia, neural tube defects (spina
bifida, anencephaly)
– Lab findings: low serum folate, hypersegmentation of
neutrophils, high FIGLU, low erythrocyte folate, high
homocysteine, macro-ovalocytosis, megaloblastic marrow,
anemia
• Assay:
– Serum folate using a microbilogic assay with Lactobacillus
casei, methyltetrahydrofolate (reflects recent intake, not
stores)
– Urine: formiminoglutamic acid (FIGLU)
Water-Soluble Vitamins
6. Vitamin B12 (Cobalamin)
• Function: Folate metabolism and DNA synthesis, maintenance of
myelinization of spinal tracts, synthesis of succinate from
methylmalonate and the synthesis of methionine from
homocysteine
• Deficiency: Megaloblastic anemia, neuropsychiatric disorder due
to demyelinization
– Strict vegetarians, D. latum infection, sprue, celiac disease
– Cobalamin deficiency results in increased levels of
methylmalonate and homocysteine
• Assay: serum vitamin B12 by Lactobacillus leichmanni competitive
protein binding assay (CPBA), plasma homocysteine, urine
methymalonic acid
• Absorption in the ileum is mediated by intrinsic factor produced by
stomach parietal cells
Water-Soluble Vitamins
6. Vitamin B12 (Cobalamin)
• Cobalamin is a cobalt-containing molecule present only in
animal products, including meat, especially liver, milk, cheese,
eggs, and other animal proteins
• Transcobalamin are transport proteins of vitamin B12 in the
plasma
• Exists as three forms in the plasma: hydroxocobalamin,
methylcobalamin and deoxyadenosylcobalamin
• Pernicious anemia: autoimmune condition characterized by
impaired absorption of vitamin B12
• Schilling's test: measures capacity to absorb vitamin B12
through administration of radiolabeled oral and parenteral
vitamin B12.
Water-Soluble Vitamins
7. Biotin
• Function: Cofactor in carboxylation reactions
• Deficiency: Rare. Caused by lack of biotin in total parenteral
nutrition. Also, avidin in raw egg whites binds biotin in gut,
preventing absorption. Dermatitis, glossitis, hair loss,
anorexia, depression, and hypercholesterolemia
• Like vitamin K, may be produced by bacteria in the gut
8. Pantothenic acid (vitamin B3)
• Function: part of coenzyme A (CoA) and of acyl carrier
protein (ACP)
• Deficiency: No syndrome recognized
Water-Soluble Vitamins
9. Ascorbic Acid (Vitamin C)
• A powerful reducing agent that is involved in many oxidation–
reduction reactions and in the transfer of protons
• Function: Many redox reactions, fsynthesis of chondroitin
sulfate and in formation of the hydroxyproline of collagen,
conversion of tyrosine to cathecolamines, wound healing
• Deficiency: Scurvy characterized hemorrhagic disorders,
including swollen, bleeding gums and impaired wound healing
• Toxicity: gastric and intestinal irritation or kidney stones, and
may interfere with copper metabolism
Water-Soluble Vitamins
9. Ascorbic Acid (Vitamin C)
• Obtained exclusively from the diet (produced
by lower mammals)
• Sources: Fruits and vegetables: Citrus fruits,
red and green peppers, strawberries,
tomatoes, broccoli, potatoes, green leafy
vegetables
• Increase the absorption of iron
• Assay: 2,4-dinitrophenylhydrazine (DNPH)
method