This document provides an overview of pharmacology of vitamins. It defines vitamins, classifies them as fat-soluble or water-soluble, discusses their history of discovery. It then covers the epidemiology of common vitamin deficiencies in India and describes various vitamins (A, D, E, K, B1, B2, B3, B5, B6, B12, and folic acid) in detail, including their sources, functions, deficiencies, uses, dosages and toxicity. The document aims to educate about the essential roles and clinical implications of vitamins.
3. 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".
5. Vitamine to vitamin. The early years
of discovery
Clinical Chemistry 43, No. 4, 1997
In 1897 Christiaan Eijkman
-Professor of physiology
whose demonstration that
beriberi is caused by poor
diet led to the discovery of
vitamins
6. Vitamine to vitamin. The early years
of discovery
In 1911 Casimir Funk isolated a
pyrimidine - related concentrate
from rice polishing
His 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”
7. 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”
8. 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
9. 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)
11. 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
12. Uses :-
1. Tretinoin(all trans-retinoic acid) and adapalene, isotretinoin,
tazarotene (synthetic retinoid) -acne vulgaris
2. Alitretinoin -kaposi’s sarcoma
3. Beta-carotene –in skin photosensitivity in erythropoietic
protoporphyria
4. Retinoic acid – oral leucoplakia and tretinoin – promyelocytic
leukemia
5. 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
13. Vitamin D
Storage forms (Prohormones) :
vitamin D2(ergocalciferol)
vitamin D3(cholecalciferol)
Active forms (Hormones) :
1,25(OH)2 ergocalciferol
calcitriol
Sources :-
Fish liver oil, milk products
Laboratory value: adult -
Calcitriol : 15-75 pg/ml
Calcidiol : 30-100 ng/ml
14. 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
15. 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
16. 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
17. 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
18. 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
19. :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
20. Vitamin K
Types with sources:-
1. Vitamin K1( phytonadione) : green leafy vegetables
2. Vitamin K2( farnoquinone) : product of metabolism of
bacteria
3. 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
21. Vitamin K Cycle and connection to
clotting pathways
Valchev et al. 2008, Furie et al. 1999
22. 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
23. Deficiency :-
Liver disease
Obstructive jaundice
Malabsorption syndrome
Prolonged broad spectrum
antimicrobial therapy
Prolonged use of sulpha drugs
Uses :-
1. Deficiency state of vitamin K
2. Hemorrhagic disease of
newborn
3. Prolonged high dose salicylate
therapy
4. Overdose of oral
anticoagulants
Dose : 50-100 mcg/day
24. 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)
25. 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
26. 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)
27. 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
28. Vitamin B2(Riboflavin)
Sources :-
dairy products, cereals, breads, fish, eggs, legumes
riboflavin 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
stomatitis
Late – corneal vascularization, anemia and personality
changes
29. 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
patients
Functions:
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
30. 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
31. Uses:
Treatment of pellagra
Nicotinic acid – hypolipidaemic
- in peripheral vascular
disease
32. 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
33. 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
35. 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
36. 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
37. 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
38.
39. 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
40. 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
41.
42. 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
43. 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, anorexia
infants – hypotonia, lethargy, apathy, alopecia
44. 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
45. 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
46. 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