Chapter Notes: Vitamins

Table of Contents
1. Introduction
2. Classification of vitamins
3. General differences: fat-soluble vs water-soluble vitamins
4. Summary table: major vitamins - active forms, sources, daily requirements, functions and deficiency manifestations
5. Water-soluble vitamins - details and important notes
6. Fat-soluble vitamins - details and important notes
7. Selected clinical and biochemical notes
8. Practical recommendations and public health points
9. Concluding summary
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Introduction

The term vitamin was introduced from the word vita (life). Early workers thought these essential nutrients were amines and used the name "vitamine"; later the final "e" was dropped when it became clear not all were amines. Vitamins are a group of organic compounds required in very small amounts for normal growth, metabolism and maintenance of health. Most cannot be synthesised in adequate amounts by humans and therefore must be obtained from the diet or, in some cases, from intestinal microflora. Vitamins are broadly classified by their solubility into water-soluble and fat-soluble vitamins.

Classification of vitamins

• Water-soluble vitamins
  • Vitamin B complex: thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin, folic acid (B9), cobalamin (B12)
  • Vitamin C (ascorbic acid)
• Fat-soluble vitamins: vitamin A (retinol and provitamin β-carotene), vitamin D (cholecalciferol), vitamin E (tocopherols), vitamin K (phylloquinone and menaquinone)

General differences: fat-soluble vs water-soluble vitamins

• Solubility and storage: water-soluble vitamins are generally not stored (except vitamin B12) and require more frequent intake; fat-soluble vitamins are absorbed with dietary lipids, are stored in liver and adipose tissue, and therefore require less frequent intake.
• Functions: water-soluble vitamins commonly serve as precursors of coenzymes and antioxidants; fat-soluble vitamins act as hormones or hormone-like regulators, antioxidants and cofactors in diverse processes.
• Toxicity: excess water-soluble vitamins are often excreted in urine and are usually less toxic; excess fat-soluble vitamins are more likely to accumulate and can cause toxicity.

Summary table: major vitamins - active forms, sources, daily requirements, functions and deficiency manifestations

Water-soluble vitamins - details and important notes

Thiamine (Vitamin B1)

Structure and active form: thiamine contains a pyrimidine ring linked to a thiazole ring. The active coenzyme form is thiamine pyrophosphate (TPP).

Functions: TPP is required for oxidative decarboxylation reactions (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase), transketolase reactions in the pentose phosphate pathway, and therefore central to carbohydrate metabolism, energy production and normal nervous function. Acetyl-CoA formed by pyruvate dehydrogenase is also precursor for synthesis of acetylcholine and for myelin synthesis.

Sources: unrefined cereals, whole grains, meat, nuts, green vegetables, eggs. Polished rice and white bread are poor sources.

Requirement: 1.0-1.5 mg/day for adults; increases with carbohydrate-rich diets, muscular activity, pregnancy and lactation.

Deficiency: causes beriberi (dry-peripheral neuropathy and muscle wasting; wet-cardiovascular involvement with oedema and heart failure), infantile beriberi and Wernicke-Korsakoff syndrome in chronic alcoholism. Early symptoms include anorexia, nausea, mental confusion, peripheral neuritis and muscle weakness.

Antimetabolites and interactions: thiaminase in raw fish and certain seafoods destroys thiamine.

Assay: erythrocyte transketolase activity (TPP-dependent) is used to detect deficiency.

Riboflavin (Vitamin B2)

Active forms: FMN and FAD, cofactors for many oxidoreductases (flavoproteins).

Functions: essential for redox reactions in carbohydrate, lipid and amino acid metabolism and for the electron transport chain. Riboflavin is needed for maintenance of mucosal, ocular and skin tissues.

Sources: yeast, germinated seeds, green leafy vegetables, milk and milk products, eggs, liver and meat. Cereals are poor sources.

Requirement: 1.3-1.7 mg/day for adults; increases with growth, pregnancy and lactation.

Deficiency: cheilosis, glossitis (magenta tongue), dermatitis and corneal vascularisation. Riboflavin status can be measured by erythrocyte glutathione reductase activity (FAD-dependent).

Niacin (Vitamin B3)

Active forms: NAD⁺ and NADP⁺. Niacin may be present in the diet as nicotinic acid or nicotinamide; tryptophan can supply a small proportion of niacin (approximately 60 mg tryptophan → 1 mg niacin equivalent).

Functions: cofactors for many dehydrogenases and reductases involved in energy-yielding oxidation and reductive biosynthesis (glycolysis, TCA cycle, fatty acid oxidation, pentose phosphate pathway, cholesterol and fatty acid synthesis).

Sources: yeast, liver, legumes, meats. Requirement: 15-20 mg/day. Tryptophan provides some niacin via conversion pathways.

Deficiency: pellagra-dermatitis (photosensitive), diarrhoea, dementia. Toxicity at high pharmacological doses (nicotinic acid, not nicotinamide) causes flushing, vasodilation and potential liver damage; nicotinic acid in gram doses is used therapeutically to lower cholesterol.

Pantothenic acid (Vitamin B5)

Active forms: Coenzyme A (CoA-SH) and acyl carrier protein (ACP); pantothenic acid is a component of the CoA structure.

Functions: transfer and activation of acyl groups; essential for TCA cycle, fatty acid oxidation and synthesis, cholesterol synthesis and ketone body utilisation.

Sources: eggs, liver, yeast, wheat germ, cereals. Requirement: approximately 5-10 mg/day.

Deficiency: rare; experimentally associated with burning feet syndrome and general weakness. Wide distribution in foods makes deficiency uncommon.

Pyridoxine (Vitamin B6)

Forms: pyridoxine, pyridoxal and pyridoxamine, interconvertible; active form is pyridoxal phosphate (PLP).

Functions: PLP is a coenzyme in numerous reactions of amino acid metabolism: transamination, decarboxylation (synthesis of neurotransmitters such as serotonin, dopamine, histamine), non-oxidative deamination, trans-sulfuration (cysteine synthesis), condensation reactions (δ-aminolevulinic acid synthesis for haem), and is covalently bound in glycogen phosphorylase. PLP is required for niacin synthesis from tryptophan.

Sources: yeast, unrefined cereals, pulses, meat, fish, potatoes, vegetables. Requirement: 1.6-2.0 mg/day; increases in pregnancy and lactation.

Deficiency: rare; causes neurological symptoms (depression, irritability, peripheral neuropathy), hypochromic microcytic anaemia (reduced haem synthesis) and, in infants, seizures due to reduced GABA. Certain drugs (isoniazid, penicillamine) can inactivate PLP causing deficiency.

Assay: erythrocyte transaminase activities (AST, ALT) are indicators of B6 status.

Biotin (Vitamin B7)

Structure/active form: enzyme-bound biotin (biocytin); biotin is covalently attached to lysine residues of carboxylases.

Functions: coenzyme for carboxylation reactions-acetyl-CoA carboxylase (fatty acid synthesis), pyruvate carboxylase (gluconeogenesis), propionyl-CoA carboxylase (propionate → succinate), β-methylcrotonyl-CoA carboxylase (branched chain amino acid catabolism).

Sources: liver, kidney, egg yolk, vegetables and intestinal bacterial synthesis. Requirement: suggested ~150-300 µg/day; most people obtain adequate amounts from diet and gut flora.

Deficiency: rare; can occur after prolonged antibiotic use or from consumption of raw egg white (avidin binds biotin), resulting in dermatitis, alopecia, nausea and muscle pain.

Folic acid (Vitamin B9)

Structure and active form: folic acid consists of pteridine, p-aminobenzoic acid (PABA) and glutamate(s); the active coenzyme is tetrahydrofolate (THF) and its one-carbon derivatives (N⁵-methyl THF, N⁵,N¹⁰-methylene THF etc.).

Functions: THF carries one-carbon units (methyl, methylene, formyl, formimino) required for synthesis of purines and thymidylate (dTMP) and for amino acid interconversions (serine ↔ glycine) and histidine catabolism. It is central to DNA and RNA synthesis and therefore important for rapidly dividing cells.

Sources: green leafy vegetables, liver, yeast. Requirement: ~200 µg/day; higher during pregnancy and lactation.

Deficiency: megaloblastic anaemia (impaired DNA synthesis, leading to large immature erythroid precursors), neural tube defects in foetus (maternal folate deficiency in early pregnancy), accumulation and urinary excretion of FIGLU (formiminoglutamate), hyperhomocysteinaemia (risk factor for cardiovascular disease).

Cobalamin (Vitamin B12)

Structure and active forms: complex corrin ring with cobalt; active coenzymes are methylcobalamin and deoxyadenosylcobalamin.

Functions:

• Isomerisation of methylmalonyl-CoA to succinyl-CoA (requires deoxyadenosylcobalamin) - important for catabolism of odd-chain fatty acids and certain amino acids.
• Methylation of homocysteine to methionine (requires methylcobalamin) and links with folate metabolism (regeneration of free THF from N⁵-methyl THF).

Absorption and storage: dietary B12 is only in animal foods. Absorption requires intrinsic factor (IF) secreted by gastric parietal cells; B12-IF complex is absorbed in the ileum via receptor-mediated, Ca²⁺-dependent uptake. B12 is transported bound to transcobalamin proteins and stored predominantly in the liver (several milligram stores sufficient for years).

Sources: meat, fish, egg, milk and dairy; absent in plant foods (strict vegetarians are at risk).

Requirement: ~3 µg/day for adults.

Deficiency: pernicious anaemia (autoimmune destruction of parietal cells or lack of IF), megaloblastic anaemia (functional folate deficiency via the "folate trap"), methylmalonic aciduria (excretion of methylmalonic acid), neuropathy (demyelination, numbness, ataxia, dementia).

Folate trap (functional folate deficiency): when B12 is deficient, N⁵-methyl THF cannot be converted to free THF (B12 required to transfer the methyl group from N⁵-methyl THF to homocysteine), so folate becomes trapped as N⁵-methyl THF and is unavailable for nucleotide synthesis, producing a functional folate deficiency.

Vitamin C (Ascorbic acid)

Structure/active form: a six-carbon lactone (ascorbic acid) - active as the reduced form.

Functions: strong reducing agent and antioxidant; required for hydroxylation of proline and lysine residues during collagen biosynthesis (critical for collagen cross-linking and strength), synthesis of certain neurotransmitters (e.g., noradrenaline), steroid metabolism, carnitine synthesis, bile acid formation and in the degradation of tyrosine derivatives. It facilitates non-haem iron absorption by reducing Fe³⁺ to Fe²⁺. Vitamin C regenerates oxidised vitamin E and acts as an antioxidant that may limit nitrosamine formation in the gut.

Sources: citrus fruits, amla, strawberries, tomatoes, leafy vegetables, potatoes. Cereals and dairy are poor sources. Most animals synthesise ascorbic acid but humans lack gluconolactone oxidase and need dietary vitamin C.

Requirement: ~60-70 mg/day; higher during pregnancy and lactation.

Deficiency: scurvy - bleeding gums, loose teeth, poor wound healing, bone abnormalities, bruising and anaemia due to impaired collagen synthesis and fragile capillaries.

Therapeutic note: vitamin C does not reliably prevent the common cold but may reduce duration and severity; large doses (>2-3 g/day) can cause diarrhoea and may increase risk of oxalate kidney stones.

Fat-soluble vitamins - details and important notes

Vitamin A (retinoids and provitamin β-carotene)

Forms: retinol (alcohol), retinal (aldehyde) and retinoic acid (acid) are biologically active retinoids. β-Carotene (a carotenoid) is a provitamin that can be cleaved to yield two molecules of retinal.

Functions:

• Vision: 11-cis-retinal bound to opsin forms rhodopsin (rod cells) and equivalent pigments in cones; photoisomerisation to all-trans retinal initiates vision signalling (Wald's visual cycle). Vitamin A is essential for dark adaptation; deficiency increases dark adaptation time and leads to night blindness.
• Regulation of gene expression and cell differentiation: retinoic acid binds nuclear receptors to regulate genes involved in growth, differentiation (epithelial cells, spermatogenesis), and embryonic development.
• Maintenance of epithelial surfaces and mucus secretion; β-carotene acts as an antioxidant.

Sources: fish liver oils (cod liver oil), liver, milk and dairy, dark-green leafy vegetables, carrots and yellow/red fruits (β-carotene). Retinol is animal-derived; β-carotene is plant-derived.

Requirement: 800-1000 retinol equivalents/day for adults (1 retinol equivalent = 1 mg retinol = 6 mg β-carotene).

Deficiency: night blindness, xerophthalmia, Bitot's spots, keratomalacia, keratinisation of epithelium, increased susceptibility to infections, growth retardation. Severe, prolonged deficiency causes irreversible blindness from corneal destruction.

Toxicity: hypervitaminosis A causes nausea, vomiting, alopecia, skin changes, bone and joint pain, hepatomegaly and weight loss; teratogenic effects in pregnancy. Excess carotenoids are not toxic but cause carotenosis (yellowing of skin).

Therapeutic uses: retinoic acid derivatives are used in dermatology (acne, psoriasis) because of effects on epithelial differentiation.

Vitamin D (cholecalciferol and ergocalciferol)

Forms: vitamin D₃ (cholecalciferol) is synthesised in skin from 7-dehydrocholesterol by ultraviolet light and obtained from animal foods; vitamin D₂ (ergocalciferol) is formed by irradiation of ergosterol in plants or produced artificially.

Activation: cholecalciferol is hydroxylated in the liver to 25-hydroxycholecalciferol, then in the kidney by 1α-hydroxylase to 1,25-dihydroxycholecalciferol (calcitriol), the hormonally active form.

Functions: calcitriol acts via a nuclear receptor (steroid-like mechanism) to maintain plasma calcium and phosphate concentrations by:

• Increasing intestinal absorption of Ca²⁺ and phosphate (induces calbindin),
• Stimulating renal reabsorption of Ca²⁺ and phosphate,
• Mobilising calcium and phosphate from bone and promoting bone mineralisation.

Sources: sunlight-induced synthesis in skin, cod liver oil, fatty fish, egg yolk. Requirement: ~200-400 IU/day.

Deficiency: rickets in children (poor mineralisation of growing bone causing bowed legs, pigeon chest, rachitic rosary), osteomalacia in adults (demineralisation and bone pain), hypocalcaemia. Renal rickets (renal osteodystrophy) results from impaired kidney activation of vitamin D. Vitamin D-resistant rickets may occur due to receptor defects or impaired hydroxylase activity.

Toxicity: prolonged high intakes produce hypercalcaemia, leading to calcification of soft tissues and kidney stones.

Vitamin E (tocopherols)

Forms: a group of tocopherols and tocotrienols; α-tocopherol is the most biologically active form.

Functions: lipid-soluble antioxidant that prevents peroxidation of polyunsaturated fatty acids in membranes and lipoproteins; protects erythrocytes from oxidative haemolysis and helps prevent oxidation of LDL (possible anti-atherogenic effect).

Sources: vegetable oils (wheat germ, corn, soya), nuts, seeds, fish, eggs and leafy vegetables. Requirement: about 8-10 mg/day (varies by source; 1 mg α-tocopherol ≈ 1.5 IU).

Deficiency: rare in humans; major sign is haemolytic anaemia due to increased RBC fragility. Retrolental fibroplasia in premature infants has been associated with vitamin E deficiency in some settings. Toxicity is uncommon.

Vitamin K (phylloquinone and menaquinone)

Forms: phylloquinone (vitamin K₁) from plants and menaquinones (vitamin K₂) synthesised by micro-organisms; synthetic menadione (K₃) is water-soluble.

Functions: required for γ-carboxylation of glutamic acid residues in certain proteins (prothrombin II, clotting factors VII, IX, X and osteocalcin in bone). This vitamin-dependent carboxylase enables these proteins to bind Ca²⁺ and become functionally active in coagulation and bone matrix formation.

Sources: green leafy vegetables (cabbage, spinach), tomatoes, cheese, meat, egg yolk; also synthesised by intestinal bacteria. Requirement: ~70-140 µg/day.

Absorption & storage: fat-soluble vitamins require bile salts for absorption and are transported in chylomicrons to the liver; vitamin K is stored in the liver. Menadione (K₃) is water-soluble and absorbed without bile salts.

Deficiency: results in bleeding tendency (increased clotting time) and haemorrhagic disease; seen in newborn infants (low placental transfer and sterile gut), after prolonged antibiotic therapy (sterilising gut flora), fat malabsorption or biliary obstruction, and in severe liver disease.

Therapeutic use: vitamin K is used to reverse anticoagulant (warfarin/dicoumarol) effects and treat haemorrhagic conditions due to deficiency.

Toxicity: excessive doses may cause haemolytic anaemia and jaundice in infants; overall toxicity is uncommon with natural vitamins.

Selected clinical and biochemical notes

• Assay methods:
  • Thiamine: erythrocyte transketolase activity (TPP-dependent).
  • Riboflavin: erythrocyte glutathione reductase (FAD-dependent) activity.
  • Pyridoxine: erythrocyte transaminase activities (AST/ALT) reflect PLP status.
  • Folate deficiency: accumulation and urinary excretion of FIGLU after histidine load.
  • Vitamin B12 deficiency: increased methylmalonic acid in urine and plasma; low serum B12; detection of intrinsic factor antibodies for pernicious anaemia.
• Drug-vitamin interactions:
  • Isoniazid and penicillamine may inactivate pyridoxal phosphate (vitamin B6) and cause deficiency unless pyridoxine supplementation is provided.
  • Anticoagulants (warfarin, dicumarol) antagonise vitamin K action and are reversible by vitamin K administration.
  • Large doses of nicotinic acid can cause flushing and hepatotoxicity.
• Antinutritional factors:
  • Thiaminase in raw fish destroys thiamine.
  • Avidin in raw egg white binds biotin and prevents its absorption.

Practical recommendations and public health points

• A balanced diet including cereals (preferably unrefined), legumes, vegetables, fruits, animal foods (where culturally accepted) and dairy usually supplies adequate vitamins.
• Pregnant and lactating women need increased intakes of folate, vitamins A, C and some B vitamins; folate supplementation before conception and during early pregnancy reduces neural tube defects.
• Strict vegetarians and vegans should monitor vitamin B12 status; supplementation or fortified foods are often necessary.
• Sunlight exposure helps maintain vitamin D status; dietary sources and supplements should be used when sunlight is insufficient (e.g., in high latitudes, indoor lifestyles or dark skin pigmentation).
• Excessive intake of fat-soluble vitamins should be avoided because of toxicity risk; water-soluble vitamins are safer at higher intakes but very large doses can have adverse effects.

Concluding summary

Vitamins are essential micronutrients with specific biochemical roles - most commonly as coenzymes, cofactors or regulators of gene expression and metabolism. Understanding their active coenzyme forms, major dietary sources, physiological functions and deficiency manifestations is important for clinical nutrition and public health. Reasoned supplementation and food fortification can prevent many deficiency disorders, while awareness of toxicity risks is needed when using pharmacological doses of fat-soluble vitamins.