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• DEFINITION• CLASSIFICATION• HISTORY• EPIDEMIOLOGY• VITAMINS IN SEGMENTS• TAKE HOME MESSAGE
DEFINITION
• Vitamins are essential organic compounds that are required in very small amount and are involved in fundamental functions in the body, such as growth, maintenance of health, and metabolism.
• The word "vitamin" comes from the Latin word vita, means "life".
ClassificationFAT SOLUBLE WATER SOLUBLE
AD E K
B1- Thiamine B2 - Riboflavin B3 – Niacin B5 – Pantothenic acid B6 –Pyridoxine B7 – Biotin B9-Folic acid B12 -CyanoCobalamine C vitamin (ascorbic acid)
Vitamine to vitamin. The early years of discovery
Clinical Chemistry 43, No. 4, 1997
In 1897 Christiaan Eijkman -Professor of physiology whose demonstration thatberiberi is caused by poor diet led to the discovery of vitamins
Vitamine to vitamin. The early years of discovery
In 1911 Casimir Funk isolated a pyrimidine - related concentrate from rice polishingHis analysis indicated that the concentrate contained nitrogen in a basic form and was probably an amine. Since it appeared to be vital to life, Funk named it “vitamine”
Vitamine to vitamin. The early years of discovery
• In 1920, Jack Cecil Drummond suggested that, since there was no evidence to support Funk’s original idea that these indispensable dietary constituents were amines, the final “e” be dropped and to have a name ending in “in”
Epidemiology of common vitamin deficiencies in India
• Prevalence of vitamin A deficiency in India is among the highest in the world
• It is the cause of blindness in 24% of children in blind schools of India
• In case of vitamin D, it has been estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency
• There is widespread prevalence of varying degrees (50- 90%) of vitamin D deficiency with low dietary calcium intake in Indian population
Bhattacharjee.et.al .Indian Journal of Ophthalmology.2008; 56 (6)
Journal of the Associations of the Physicians in India november 2011 v oL . 59
Vitamin A Three forms :-
retinol, retinal and retinoic acid Sources :-
animal – retinol
vegetable – provitamins ( carotenes) which are converted to vitamin A in liver
Normal Laboratory value :adult – 20-100 mcg/dl Functions :-
• Control gene expression through two type of transcription receptors – RAR
(retinoic acid receptor) and RXR (retinoid X receptor)
• Control epithelial cell proliferation and differentiation(retinoic acid)
• Formation of rhodopsin for night vision(retinal)
Deficiency :-
Causes : Inadequate dietary intake Pregnancy Lactation Mal-absorption syndrome Hepato-biliary disease
Deficiency :-Manifestations:
• Xerophthalmia -involves xerosis (dryness)
of eye, ‘bitot’s spots’, keratomalacia (softening
of cornea), corneal opacities, night blindness
(nyctalopia) progressing to total blindness
• Dry and rough skin with papules, hyperkeratinization
• Keratinization of bronchopulmonary epithelium,
increased susceptibility to infection
• Diarrhea due to unhealthy gastrointestinal
mucosa
• Growth retardation
Uses :-1. Tretinoin(all trans-retinoic acid) and adapalene, isotretinoin,
tazarotene (synthetic retinoid) -acne vulgaris2. Alitretinoin -kaposi’s sarcoma3. Beta-carotene –in skin photosensitivity in erythropoietic
protoporphyria4. Retinoic acid – oral leucoplakia and tretinoin – promyelocytic
leukemia5. Acitretin and tazarotene -psoriasis
-Isotretinoin and acitretin -teratogenic activity 6. Children with measles are given vitamin A
Prophylaxis : 4000 IU/day, treatment : 50000-100000 IU/day Toxicity : 100000 IU/day for more than 3 weeks
Vitamin D Storage forms (Prohormones) :
vitamin D2(ergocalciferol)vitamin D3(cholecalciferol)
Active forms (Hormones) :1,25(OH)2 ergocalciferolcalcitriol
Sources :- Fish liver oil, milk productsLaboratory value: adult -Calcitriol : 15-75 pg/mlCalcidiol : 30-100 ng/ml
Functions :-• Intestinal absorption of calcium and phosphorus
• Mineralization of bones
• Renal retention of calcium and phosphorus
•Maturation and differentiation of mononuclear cells
•Influences cytokine production and immune function
Causes of impaired vitamin D action:
• Vitamin D deficiency• Impaired cutaneous
production• Dietary absence• Malabsorption Accelerated loss of
vitamin D• Increased metabolism
(barbiturates, phenytoin, rifampin)
• Impaired enterohepatic circulation
• Nephrotic syndrome
• Impaired 25-hydroxylation
• Liver disease, isoniazid Impaired 1 alpha-
hydroxylation• Hypoparathyroidism• Renal failure• Ketoconazole• 1 alpha-hydroxylase mutation Target organ resistance• Vitamin D receptor mutation• Phenytoin
Deficiencies :-
In children, vitamin D deficiency causes rickets
In adults, vitamin D deficiency leads to osteomalacia, causing bone pain and muscle weakness
Dose : 200-400 IU/day
Toxicity: >50000IU/day
Uses :-
1. Rickets in children :
a)Vitamin D resistant rickets
(Vitamin D receptor mutation),
b)Vitamin D dependent rickets
(Renal 1alpha-hydroxylase mutation),
c)Renal rickets
2. Osteomalacia in adult
3. Hypoparathyroidism
4. Calcipotriol-in plaque type psoriasis
Vitamin E
Chemistry Alpha tocopherol - most abundant and potent Source :-Cottonseed oil, corn oil, sunflower oil, wheat germ oil – richest source Normal Laboratory value :adult - 5-18 mcg/ml Function: Vitamin E protects red blood cells as an antioxidant and helps
utilization of vitamin A Manifestations of deficiency :- Muscular dystrophy Hemolytic anemia Hepatic necrosis
:Uses -1.Vitamin E deficiency
2.G-6-PD deficiency
3.Acanthocytosis
4.Retrolental fibroplasia in premature infants
5.Hypervitaminosis A
6.Intermittent claudication
7.Nocturnal muscle cramps
Adult : 400 mg/day, children : 200 mg/day
Vitamin K Types with sources:-
1. Vitamin K1( phytonadione) : green leafy vegetables2. Vitamin K2( farnoquinone) : product of metabolism
of bacteria3. Vitamin K3( menadione) : synthetic analogue, three
times more potent Normal Laboratory value: adult – 0.13-1.19 ng/ml Function Helps in Blood Clot Formation Vitamin K2 plays an important role in
bone formation Vitamin K Prevents Cardiovascular
Disease
Vitamin K is a cofactor for the formation of gamma-carboxyglutamic
acid residues on coagulation proteins just like prothrombin, factor VII,
IX and X
Vitamin K antagonist :- Warfarin, dicumarol and acenocoumarol ( oral anticoagulants)
Contraindicated in pregnancy – fetal warfarin syndrome
In maintenance therapy of acute DVT or pulmonary embolism
following an initial course of heparin
Preventing venous thromboembolism in patients undergoing
orthopedic or gynecological surgery, recurrent coronary ischemia in
patients with acute myocardial infarction
Vitamin K and The Clotting Cascade
Deficiency :-Liver diseaseObstructive jaundiceMalabsorption syndromeProlonged broad spectrum antimicrobial therapy Prolonged use of sulpha drugs Uses :-1. Deficiency state of vitamin K2. Hemorrhagic disease of
newborn3. Prolonged high dose salicylate
therapy4. Overdose of oral
anticoagulants Dose : 50-100 mcg/day
Vitamin B1(Thiamine) Sources :-
-whole grains, pulses, nuts, green vegetables, yeasts, eggs and meat
-tea, coffee, raw fish and shellfish contain thiaminase that destroys thiamine
Normal Laboratory value: adult – 0-2 mcg/dl
Functions :-• Thiamine phosphate, active form of thiamine, serves as a cofactor
for several enzymes involved in carbohydrate catabolism • It also helps in the hexose monophosphate shunt that generates
nicotinamide adenine dinucleotide phosphate (NADP) and pentose for nucleic acid synthesis
• Synthesis of acetylcholine and gamma-aminobutyric acid (GABA)
Deficiency :-Causes : Poor dietary intake Alcoholism Advanced gastric cancer Prolonged hyper emesis gravidarum Prolonged anorexia Bariatric bypass surgery for morbid obesity Chronic diuretic therapy Polished rice based diets
Manifestations :• Early stage – anorexia, irritability, decrease in short term memory
• Prolonged deficiency – beriberi• dry (neuritic) type and wet (cardiac) type
• Alcoholics – wernicke’s encephalopathy
• TRMA(thiamine responsive megaloblastic anemia)
Uses
1. Treatment and prevention of thiamine
deficiency, including a specific disorder
called Wernicke-Korsakoff syndrome
(WKS) that is related to low levels of
thiamine (thiamine deficiency) and is
often see in alcoholics
2. Correcting problems in people with
certain types of genetic diseases
including Leigh's disease, maple syrup
urine disease, and others
Vitamin B2(Riboflavin) Sources :-
dairy products, cereals, breads, fish, eggs, legumesriboflavin is extremely sensitive to light
Normal Laboratory value: adult – 4-24 mcg/dl
FAD(flavin adenine dinucleotide) and FMN(flavin mononucleotide) – cofactor in oxidation-reduction reactions, important for metabolism of carbohydrate, protein and fat
Deficiency :-Early – cheilosis, seborrhoea, magenta tongue, angular stomatitisLate – corneal vascularization, anemia and personality changes
Vitamin B3(Niacin) Sources :-
liver, meat, fish, cereal husk, nuts, pulses Nicotinic acid :-
Hypolipidemic agent – lowers LDL-C and triglycerides, increases HDL-C
Profound adverse effects profile Contraindicated in pregnancy, peptic ulcer, diabetic and gout
patientsFunctions:
Nicotinic acid and nicotinamide are biologically active derivatives -- precursors of two coenzymes, nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), important in numerous oxidation-reduction reactions and adenine diphosphate–ribose transfer reactions involved in DNA repair and calcium metabolism
Deficiency :- Pellagra :
(pelle = skin, agra = rough)
Found in –population eating
high corn-based diet
-- Alcoholics
-- Hartnup disease
-- Carcinoid syndrome
Characterized by dermatitis,
diarrhea and dementia
Incidence more in women
Vitamin B5(Pantothenic acid) Sources: liver, mutton, whole grains, egg yolk and vegetables
Component of co-enzyme A; - Involved in carbohydrate, fat, steroid and porphyrin
metabolism- Heme synthesis- Formation of ketone bodies- Acetylcholine formation- Citric acid formation, TCA cycle starter
No clinical deficiency
Vitamin B6(Pyridoxine) Sources :
liver, meat, egg, soybean, vegetables and whole grain
Normal Laboratory value: adult – 5-30 ng/ml
Functions:Pyridoxal phosphate acts as a coenzyme in – Synthesis of nonessential aminoacids Tryptophan and sulphur containing amino acid metabolism Formation of 5-HT, dopamine, histamine, GABA and amino-
levulinic acid
Deficiency :-Causes Isoniazid causes pyridoxine deficiency Hydralazine, cycloserine and penicillamine interfere pyridoxine utilization Oral contraceptivesManifestations :Seborrheic dermatitisGrowth retardationMental confusionConvulsionPeripheral neuritisSideroblastic anemia
High intake – sensory neuropathy and dependence
Promote peripheral decarboxylation of levodopa
Vitamin B12 Sources :- Just animal source – liver, kidney, sea fish, egg yolk, meat and
dairy products Laboratory value : adult –279-996 pg/ml
Functions :- Conversion of homocysteine to methionine – protein synthesis Formation of S – adenosyl methionine, needful for
phospholipid and myelin synthesis Cell growth and replication
Intrinsic factor, secreted by parietal cells of gastric mucosa is required for absorption
Deficiency :-Causes :
- Addisonian pernicious anemia- Gastric mucosal damage- Malabsorption- Fish tapeworm infection of gastrointestinal tract- Strict vegetarians- Pregnancy due to increased demand
Manifestations :- Megaloblastic anemia- Glossitis, achlorhydria- Subacute combined degeneration of and spinal cord, mental changes
Dose : cyanocobalamin 100-1000 mcg/day I.M. on alternate days for 2 weeks followed by once a month; methylcobalamin 1000-1500 mcg/day oral
Folic Acid Sources :-
liver, green leafy vegetables, egg, meat, milk Normal Laboratory value: adult –(RC) 150-450 ng/ml cells
--(S) 5.4-18 ng/ml Functions :-
FA(inactive) DHFA THFA(coenzyme) by folate reductase and dihydrofolate reductase respectively mediates number of one carbon transfer reactions---
Conversion of homocysteine to methionine Generation of thymidylate – constituent of DNA Conversion of serine to glycine Purine synthesis Histidine metabolism
Deficiency :- Causes :
- Inadequate dietary intake- Malabsorption- Chronic alcoholism- Pregnancy and lactation- Prolonged therapy of anticonvulsants and oral contraceptives
Manifestations :- Megaloblastic anemia- Epithelial damage- Neural tube defects in offspring- General debility, weight loss, sterility
Prophylactic folic acid supplementation in 2nd and 3rd trimester along with vitamin K in the last month of pregnancy is recommended, in women receiving antiepileptic drugs to minimize neural tube defects and bleeding disorder respectively in the neonate
Pyrimethamine : used in combination with sulfonamide or dapsone for treatment of falciparum malaria by inhibiting plasmodial dihydrofolate reductase
Methotraxate : used in choriocarcinoma, children with acute leukemias, non-hodgkin lymphoma, breast,bladder,head and neck cancers; rheumatoid arthritis, psoriasis and as an immunosuppresant
Cotrimoxazole – bacterial folate metabolism blocker; is utilized for urinary tract infections, respiratory tract infections, pneumocystis jiroveci, chancroid and bacterial diarrhea
Dose : 1-5 mg/day
Biotin( Vitamin B7 ) Sources :
- Liver, kidney, milk and milk products, egg yolk- Vegetables, legumes and grains
Coenzyme for carboxylases required for various CO2 transfer reactions in fatty acid metabolism, aminoacid catabolism, gluconeogenesis
Deficiency occurs in :( experimental)- prolonged raw egg white intake- biotin-free total parenteral nutrition
Symptomatology : dermatitis of extremities, anemia, muscle pain, depression,
somnolence, anorexiainfants – hypotonia, lethargy, apathy, alopecia
VITAMIN C (ASCORBIC ACID) Sources :- Citrus fruits like amla, green leafy vegetables, potatoes,
tomatoes L- ascorbic acid is naturally occurring form Laboratory value for adult – 0.4-1 mg/dl Functions:- Cellular oxidation-reduction reactions Collagen synthesis Absorption of iron Formation of catecholamine,serotonin, ferritin and tetrahydrofolate Role in stress
Deficiency :-Scurvy -- Only seen in malnourished infants, children,
elderly, alcoholics and drug addicts Manifestations : - Capillary fragility increased- Delayed wound healing- Swollen gums- Poor dentine formation in children- Poor mineralization of bone- Anemia
‘Bachelor’ scurvy
Dose : prophylaxis 50-500 mg/day,Scurvy 1-1.5 gm/day
Take home message Assess the adequacy of vitamin in
your diet
If you are falling 75% below for
several vitamins, you may want to
supplement your diet with a
vitamin pill
BUT THERE IS NO SUBSTITUTE FOR
A HEALTHY DIET
The best way to get your vitamins
is through natural resources