Vitamins in Health & Disease ML Kulkarni
Page numbers followed by f refer to figures and t refer to tables
Abdomen 55
Abetalipoproteinemia 66, 67, 182
Abnormalities of immunohemato-poietic system 49
Absorption of vitamin B12 142
Acetylation of sugars 157
Activated partial thromboplastin time 85
disease 167
lower respiratory tract infections 39
pernicious beriberi 103
respiratory tract infection 1
Acyl carrier protein 157
Adolescents 40
Advanced conjunctival and corneal xerosis 26f, 27f
Alcoholic liver disease 147
Alkaline phosphatase 58
and ornithine decarboxylase 16
Alpha-tocopherol equivalent 63
Anatomical blind loop 150
Ancylostoma duodenale 19
Anemia 152
Angular stomatitis 108f
and dermatitis 95
Appetite disturbance 15
infestation 87
lumbricoides 19
Ascorbic acid 6
Aspartate aminotransferase 122
Assessment of vitamin K status 85
Ataxia with vitamin E deficiency 66, 68
Atherosclerosis 84
Atresia 87
disease 147
disorder 150
Autosomal dominant hypophosphatemic rickets 58
B-complex 6
Beriberi 95, 101f
Beta-carotene 10, 38
Betaine 182
Biliary tract obstruction 87
Biogenic amines 119t
Biotidinase deficiency 182
Biotin 5, 6, 95, 96, 136, 181, 182
Bitot's spot 8, 17, 23, 24, 31
Blood clotting 84
changes in scurvy 170
Gla protein 84
mineral content 42
Bowing of
legs 56f
long bones 59f
Breastfeeding 19
Bronchopulmonary dysplasia 1
Calcium 58
Cancer 133
Carbamazepine 89
Carbohydrate-related citric acid cycle transfer reactions 157
Carboxylation of
growth-arrest specific protein 84
nephrocalcin 84
osteocalcin 84
Carcinoid syndrome 113
Cardiovascular disease 133
Carnitine 181
Causes of
B12 malabsorption 150
vitamin K deficiency beyond infancy 87
Cefamandole 87
Cefoperazone 87
Celiac disease 87, 148
Cell membrane formation and structure 157
Cellular defects in cobalamin metabolism 148
Cephalosporins 90
flours 38
grains and products 173
Cervical dysplasia 133
Chediak-Higashi syndrome 182
Cheesy Bitot's spots 25f, 26
Cheilosis 95
Chest deformity 56f
Cholecalciferol 6, 43
Cholesterol and bile salt production 157
cholestatic hepatobiliary disorders 68
diarrhea 1
myeloid leukemia 147
disease 53
failure 58
small intestinal disease/malabsorption 87
Cirrhosis 87, 147
Classification of
vitamin 6t
K deficiency bleeding of newborn infant 89t
xerophthalmia 23t
Clinical setting of pellagra 112
Coagulation cascade 86f
Cobalamine 95, 152, 182
Coenzyme A 156
Colchicine 150
Colorectal cancer 133
Competition for cobalamin in small intestine 148
haptocorrin deficiency 147
transcobalamin deficiency 147, 150
impression cytology 29
xerosis 23, 24f, 25f, 31
Convulsions of newborn 120
scar 17, 23
ulceration 23, 27
xerosis 23, 26, 31
Corner sign 170
Coronary artery disease 1, 133
Coumarin anticoagulants 87
Counter immune electrophoresis 86
Craniotabes 55
Crohn's disease 87, 113
selective malabsorption with proteinuria 150
Cystathioninuria 120
Cystic fibrosis 66, 68, 87
Defective transport 148
Deficiency of
pantothenic acid 158
vitamin D 53
Deoxyribonucleic acid 126
Depression 95
Dermatitis 95
Determining vitamin A complications 17
Development of rickets 51
Diarrheal diseases 19
Ca deficiency 58
inadequacy protein-energy malnutrition 87
Diphyllobothrium latum 148
Disseminated intravascular coagulation 92
Distribution of vitamin A 36
Drug therapy 87
granular appearance of corneal xerosis 27f
stabilized forms 38
water-dispersible forms 38
Electroencephalogram 121
Electroimmunoassay 86
Elimination of vitamin A deficiency 36
releasing substances 6
storage 157
Epileptiform convulsions in infants 95
Estimation of folic acid 133
Etiological classification of rickets 53
Evaluation of vitamin E status 73
hypophosphatemia 57
hypophosphatemic rickets 53
Fanconi syndrome 53, 58
Fat malabsorption 66, 67
Fatigue 95
Fatty acid elongation 157
Fibrin degradation products 92
Fish tapeworm 148, 150
Five food-group system 173
adenine dinucletotide 106
mononucleotide 106
Folacin 130
Folic acid 5, 6, 95, 124, 130, 133, 181, 182
Folinic acid 182
fortification 37
group 173
Formiminoglutamic acid 152
Forms of
folic acid 130
vitamin A 9
Fresh frozen plasma 92
Functions of
pantothenic acid 156
A 13
D 47
Gallstones 87
Gastrectomy 148
atrophy 148
cancer 133
Gastroenterostomy 113
Gaucher's disease 147
Giardia lamblia 19
Global mucosal deficiency 148
Glossitis 95
Glucose-6-phosphate dehydrogenase 93
Glutaric aciduria 182
Glutathione 182
Gluten-induced enteropathy 150
Graft-versus-host disease 150
Granulomatous disease 50
Ground glass cortex 171
Gyrate atrophy with ornithinuria 120
Halo epiphysis 171
Hartnup disease 113
Hawkinsunuria 182
Heat labile 130
Hemolytic anemia 66
Hemorrhage 88
Hemorrhagic disease of newborn 88, 90
Hepatic tocopherol-binding protein 63
Hepatitis 87, 147
Hereditary hypophosphatemic rickets with hypercalicuria 58
High performance liquid chromatography 103
History of vitamins 2
HIV infection 148, 150
Holocarboxylase synthetase deficiency 182
Homocysteine 152
Homocystinuria 120
immunodeficiency virus 1
promyelocyte leukemia cell line 49
Hydantoins 87
Hypersegmentation 152
neutrophils 129f
neutrophils in megaloblastic anemia 126f
A 32
D 60
Ileal resection 148
Ileocolic fistula 150
Imerslund-Grasbeck syndrome 150
Infant formula 38
Infectious diseases 19
Interaction with
cancer cells 49
copper 16
iron 16
vitamin E 16
zinc 16
Interesting uses of vitamin C 165
absorption of vitamin E 64
parasites 19
stagnant-loop syndrome 150
stricture 150
Intramuscular vitamin K prophylaxis 92
Intraventricular hemorrhage 1
Investigation in megaloblastosis 152
Isoniazid 87
Isoprenoid biosynthesis 157
Jacobus bontius 8
Jejunal diverticulosis 150
Jejunitis 113
Juvenile pernicious anemia 148
Kearns-Sayre syndrome 182
Keratomalacia 8, 17, 28
Kidney stones 84
Korsakoff syndrome 103
Lack of sunlight 53
Lactating women 40, 81
Large oval xerophthalmic ulcer 26
Latex agglutination 86
Lipoic acid 182
Liver disease 53, 87
chain fatty acids 10
term hydroxocobalamin therapy 147
birth weight 1, 20, 51
plasma calcium 48f
Malabsorption 148
syndromes 53
Manifestations of vitamin A deficiency 21f
Marrow morphology 152
deficiency of vitamin D 51
folic acid deficiency 131
Matrix Gla protein 85, 93
Measles 1
Medical Research Council 131
Megaloblastic anemia 147, 150t
Megavitamin therapy 181
Menaquinones 6
Metabolism of vitamin
C 160
D 43
K 78
Metformin 150
Methylenetetrahydrofolate reductase 131
Methylmalonic acid 152
Milestones in discovery of vitamins 4
disorders 182
electron transport chain disorder 182
Modifications of plasma membrane glycoprotein 16
Mother to child transmission 39
Multiple gestations 51
Muscular pains 95
Myelofibrosis 147
Myeloproliferative diseases 147
N-acetylglucosamine 157
Nasolateral seborrhea 95
Nausea 95
Neomycin 150
Nerve signaling 84
Neural tube defects 131
Neuroectodermal tumors 133
Neuromuscular disorders and thrombosis 1
Neutropenia 152
Niacin 5, 6, 95, 96, 110
Nicotinamide 181, 182
adenine dinucleotide 16, 112
adenine dinucleotide phosphate 110
Nicotinic acid and nicotinamide 95, 96
Night blindness 17, 23, 23f, 31
Nutritive value of fruits 179
Oils and fats 165
Oncogenic rickets 58
leukoplakia 133
E therapy in children 75
K prophylaxis 91
Orofacial clefts 132
Oropharyngeal cancer 133
acid 152
aciduria 182
Osteocalcin 84
Osteomalacia 53
Oxidative metabolism 157
Pancytopenia 147
Pantothenic acid 5, 6, 95, 96, 154, 182
Parathyroid hormone 44, 58
Parenchymal/cholestatic disease 53
Partial gastrectomy 150
Pellagra 113f
Pelvis 55
Periodic supplementation 35
Peripheral neuropathy 95
Pernicious anemia 147, 150
Phenformin 150
Phospholipid biosynthesis 157
Phosphorus 58
Phylloquinones 6
methylmalonic acid 151
vitamin A level 17
Polychlorinated biphenols 91
Polycythemia vera 147
Polyglutamate form 130
Polyneuritis 95
Polyunsaturated fatty acids 65
Prevention of vitamin K deficiency 91
Primary hyperoxaluria 120
Prolonged nitrous oxide anesthesia 148
Protection against degenerative diseases 15
Protein 152
acetylation 157
bound glutamate 82
energy malnutrition 66
Prothrombin time 85
Pseudo hypoparathyroidism 53
Pulses and legumes 173
Pyridoxal 95, 96
phosphate 117
Pyridoxamine 6, 95, 96
phosphate 117
Pyridoxine 6, 95, 96, 117, 181, 182
phosphate 117
Pyruvate dehydrogenase deficiency 182
Rachitic rosary 54f
Radio immunoassay 86
Randomized control trials 39
Rapid weight gain 51
Recommended nutrient intakes of vitamin K 80t
Red cell folate 152
Regional ileitis 87, 148
Regulation of vitamin D synthesis 45
anomalies 132
disease 147
tubular acidosis 53
Respiratory diseases 19
Retinal 9, 10
Retinoic acid 9, 10
Retinoids 9
Retinol 9, 10
binding protein 11
acetate 38
palmitate 38
Reversal of megaloblastosis 152t
Reyes syndrome 87
Riboflavin 6, 95, 96, 105, 181, 182
Rickets 53
Rifampin 87
Role in
calcium metabolism 47
differentiation of epidermal cells 50
human metabolic processes 156
Role of
folic acid in prevention of malformations 131
A in vision 14
D on bone 47
K in bone metabolism 84
K in cell signaling and nervous system 85
Salicylates 87
Scars 29
Scheme of vitamin A metabolism 12
Schilling test 152
gums 169
rosary 171
Scurvy 170f
pancreatitis 150
protein-energy malnutrition 30
Short bowel syndrome 66, 68, 87
Sideroblastic anemia 120
Signs of rickets 55
Simple atrophic gastritis 150
Skin changes in pellagra 113f
Sleep disturbances 95
Slow-release potassium chloride 150
Sources of vitamin D 47f
Spine 55
Sprue 87
Stages of infantile beriberi 102f
biosynthesis 157
hormone production 157
Structure of
ascorbic acid 159f
biotin 136f
folic acid 124f
niacin and nicotinamide 110f
pantothenic acid 154f
pyridoxine, pyridoxal and pyridoxamine 117f
riboflavin 105f
thiamine and thiamine pyrophosphate 97f
vitamin B12 141f
Subtotal gastrectomy 113
Superficial punctate keratopathy 26f
Synthesis of
collagen 163f
plasminogen 16
retinol-binding protein 16
vitamin 87
Temporal patch of conjunctival xerosis 24f
Terminal ileum 148
Tetrahydrobiopterin 182
Tetrahydrofolate 126
Tetrahydrofolic acid 124
Thiaminases 99
Thiamine 6, 9597, 181, 182
deficiency 101f
pyrophosphate 98, 99
Thrombocytopenia 152
Thymocyte growth peptide 32
Tocopherols 6
Top feeding 51
Total parenteral nutrition 87
Tragedy of modern medicine 2
Transcobalamin 147
II deficiency 148
Treatment of vitamin A deficiency 30t
Tricarboxylic acid 156
Tropical sprue 150
Tumor induced rickets 58
Types of beta-carotene 10f
Typical foamy Bitot's spots 25f
Tyrosinemia 182
Ulceration 17
Ulcerative colitis 87
Umbilical bleed in neonate 90f
Urinary excretion test 152
Urine 152
Use of proton pump inhibitors 150
Visual cycle of vitamin A 14f
Vitamin 1
A 6, 7, 19
alcohol 9
aldehyde 9
and immunity 15
deficiency 21, 30
fortificants 38t
prophylaxis 36t
supplementation for cystic fibrosis 39
B12 6, 140
B6 95, 96, 117
C 6, 159, 181, 182
D 6, 42
deficiency 58
dependent rickets 57
receptor 45
synthesis 43f
D2 42
E 6, 62, 181, 182
and cataract 73
and myopathy 72
and neurodegenerative diseases 73
and retinopathy of prematurity 69
and selenium 72
content of vegetable oils 64t
mega doses 87
supplementation 74
K 6, 77, 182
and atherosclerosis 85
and childhood cancer 92
deficiency bleeding 88
dependent carboxylase 82
dependent proteins in blood clotting 83
epoxide cycle 82, 83
in human metabolism 84t
prophylaxis 91
Wernicke's encephalopathy 103
Wernicke-Korsakoff syndrome 95
line 171
retinal specks 28f
Widening of wrists 56f
World Health Organization 17, 40
Xanthurenic aciduria 120
Xerophthalmia 8, 22f
fundus 23, 29, 31
lesions 22f
Zinc deficiency 16
Zollinger-Ellison syndrome 150
Zone of rarefaction 171
Chapter Notes

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VitaminsChapter 1

Vitamins are organic compounds that are consumed in the diet. Most vitamins are required in small quantities and serve specific cellular functions. The word ‘Vitamin’ comes from Latin, in which “Vita” means life and “amine” means containing basic or amine nitrogen. Previously, vitamins were considered as substances just to prevent or treat deficiency states. The research in recent years has unfolded their role in many other body functions. For example, beta-carotenes, vitamin C, vitamin E are known to have antioxidant properties that prevent many degenerative disorders of adult life, like coronary artery disease (CAD), diabetes, etc. The role of periconceptional folic acid in the prevention of neural tube defect (NTD) and possibly other malformations, is the greatest discovery of this century. This has opened a new exciting field for prevention of malformation by the simple method of food supplementation.
The role of folic acid in the prevention of CAD, strokes and malignancies by correcting homocysteine metabolism has given a hope for the prevention of diseases in adults. Folic acid supplementation during pregnancy in reducing low birth weight (LBW) is of great public health importance.
The observation that vitamin A prevents morbidity and mortality in measles, acute respiratory tract infection (ARI), chronic diarrhea and has its role in the reduction of human immunodeficiency virus (HIV) transmission from mother to fetus, are the exciting contributions of studies on vitamins. Vitamin E once known only as an agent against “antifertility” is now known to have a lot of other benefits like, prevention of retinopathy of prematurity, intraventricular hemorrhage (IVH) of prematurity, bronchopulmonary dysplasia (BPD) of preterms, hemolytic anemia of preterms, myopathies, neuromuscular disorders and thrombosis.2
Tragedy of Modern Medicine
Too much zeal for the new and contempt for the old
Putting knowledge before wisdom
Putting science before art
Putting cleverness before common sense
Making cure of the disease more grevious than endurance of the disease
Treating patients as cases!!
“One swears by wholemeal bread, one by sour milk; vegetarianism is the only road to salvation of some, others insist not only on vegetables alone, but on eating those raw. At one time the only thing that matters is calories; at another time they are crazy about vitamins or about roughage. The scientific truth may be put quite briefly; eat moderately, having an ordinary mixed diet and don't worry.”
—Sir Robert Hutchison (1871–1960)
The experiences of eighteenth century explorers and the British navy that fresh fruits could cure scurvy is an important milestone in the discovery of vitamins.
The fact that such components of nutrition existed was not recognized long ago until a phase came in the science of nutrition, where it gained recognition on a global scale. It has now been agreed as a fact that, the existence of dietary factors of the nature of vitamins, was documented and came from the school of Professor Bunge at Basel.
zoom view
Sir Robert Hutchison (1871–1960)
In the year 1881, Lunin, one of the workers in that school, fed mice with an artificial component of the separate constituents of milk. He found out that after being fed with this mixture, the animals failed to survive even though proteins, fats, carbohydrates and salts were present in the mixture. It was concluded that this mixture must contain besides these three principal ingredients, another key ingredient essential for life.
History of Vitamins During the Five Periods
The history of vitamins can be divided into five periods
First Period
Healing of diseases associated with vitamin deficiency, through consumption of specific foods that help cure diseases. For example, treating night blindness with liver.
Second Period
This period was focused to induce a deficiency disease in animals. For example, ability to produce beriberi. Hopkins conceptualized finally that, “small amounts of accessory growth factors” are necessary for growth and life and the Polish-American Scientist Casimir Funk coined the term “vitamine” in 1912.
Third Period
This period was mainly concerned with the discovery, structure and synthesis of all the vitamins and ended with the synthesis of vitamin B12 in 1972. Many researchers were awarded Nobel prizes in recognition of their feats.
Fourth Period
The fourth phase was mainly concerned with the establishment of dietary requirements and commercial production of vitamins. It was during this period that most of the B-complex vitamins were identified as coenzymes. The first successful industrial effort happened during this period with the commercial synthesis of vitamin C by Reichstein in 1933.
Fifth Period
The hallmark of this period is the report stating the cholesterol lowering effect of niacin in 1955. This period is also known for the discovery of many new biochemical functions of vitamins.4
Milestones in the Discovery of Vitamins
Some of the important milestones in the discovery of vitamins are recorded in the following points and subsequent two tables (Table 1.1 and 1.2).
Mendel distinguished two types of vitamins based on their solubilities and named them fat-soluble A and water-soluble B.
The terminal alphabet ‘e’ from the word “vitamine” was dropped and the vitamins were named as vitamin A and vitamin B. Anti-scurvy factor was named as vitamin C. Anti-rickets factor was named as vitamin D. Anti-hemorrhagic factor of chicks in 1935 by Henrik Dam, was later named vitamin K.
There are many gaps present in between the alphabetical and numerical naming of the vitamins, which clearly indicate that there were many nutritional factors that were initially thought to be vitamins but were later found out to be other factors. This confusion arose due to similarities between those factors and vitamins. After the isolation of each vitamin, they were given names according to the chemical compound and the class to which they belonged. The last vitamin to be discovered was vitamin B12 in 1948.
“But further, no animal can live upon a mixture of pure protein, fat and carbohydrate and even when the necessary inorganic material is carefully supplied, the animal still cannot flourish. The animal body is adjusted to live either upon plant tissues or the tissues of other animals and these contain countless substances other than proteins, carbohydrates and fats… In diseases such as rickets and particularly in scurvy, we have had for long years knowledge of a dietetic factor; but though we know how to benefit these conditions empirically, the real errors in the diet are to this day quite obscure. They are, however, certainly of the kind which comprises these minimal qualitative factors that I am considering.”
—Sir Frederick Gowland Hopkins
(20th June 1861 to 16th May 1947)
Table 1.1   Vitamins—discovery and synthesis
Folic acid
Pantothenic acid
Table 1.2   Vitamin-related Nobel prize winners
Adolf Windaus
Research into steroid and their connection with vitamins
Christain Eijkman
For antineuritic vitamins
Sir Frederick G Hopkins
Discovery of growth-stimulating vitamin
Paul Karrer
Research on carotenoids and vitamin A
Richard Kuhn
Work on carotenoids
Edward A Doisy
Work on vitamin K
Fritz A Lipmann
Discovery of coenzyme A
Axel H T Theorell
Work on oxidation enzymes
Konrad E Bloch
Work on cholesterol and fatty acids
Ragnar A Granit
For studies on wavelength distribution in eye
Vitamins are classified according to their solubility and their role in various metabolism. A practical way of classifying them is based on their solubility. The following table 1.3 lists the classification of vitamins.
Table 1.3   Classification of vitamins
Ascorbic acid (Vitamin C)
Energy releasing substances
Thiamine (B1)
Riboflavin (B2)
Niacin (B3)
Pantothenic acid
Folic acid and vitamin B12
Pyridoxine (B6)
  • Pyridoxal
  • Pyridoxamine
Vitamin A (Retinol, β-carotene)
Vitamin D (Cholecalciferol)
Vitamin K (Phylloquinones, Menaquinones)
Vitamin E (Tocopherols)
Vitamins, as the Latin derivation of the name implies, are essential for maintenance of adequate health and life. They are diverse organic substances provided in small quantities in the diet and are found in a variety of chemical forms and structures. Vitamins have assorted essential biochemical roles in contributing towards maintenance of health and have unique therapeutic places in the treatment of related disorders.
The further section deals in detail with the individual vitamins, their history, biochemical and physiological aspects, recommended dietary allowances, deficiency states and toxicity if any, associated with them.