Vitamin B Complex

The B-complex vitamins are eight water-soluble micronutrients that function almost exclusively as coenzymes in intermediary metabolism. NEET PG loves this topic because the coenzyme form, the deficiency syndrome, the biochemical block, and a classic drug interaction are all independently testable. This note ties each vitamin to its active coenzyme, its diagnostic test, and its deficiency picture.

Overview & classification

All B vitamins are water-soluble, are not stored in large amounts (except B12, stored 3–5 years in liver), and excess is largely excreted in urine — so toxicity is rare except for B6 (pyridoxine) and B3 (niacin). Each is converted to an active coenzyme that drives a defined reaction class.

Vitamin	Common name	Active coenzyme	Core biochemical role	Classic deficiency
B1	Thiamine	Thiamine pyrophosphate (TPP)	Oxidative decarboxylation; transketolase	Beriberi, Wernicke–Korsakoff
B2	Riboflavin	FMN, FAD	Redox / electron transfer	Angular stomatitis, glossitis
B3	Niacin	NAD⁺, NADP⁺	Hydride transfer (dehydrogenases)	Pellagra (3 Ds)
B5	Pantothenic acid	Coenzyme A, ACP	Acyl group transfer	Burning feet syndrome
B6	Pyridoxine	Pyridoxal phosphate (PLP)	Transamination, decarboxylation	Sideroblastic anaemia, neuropathy, seizures
B7	Biotin	Biocytin (carboxybiotin)	CO₂ carrier (carboxylases)	Alopecia, dermatitis, acidosis
B9	Folate	Tetrahydrofolate (THF)	One-carbon transfer	Megaloblastic anaemia, NTDs
B12	Cobalamin	Methyl-/adenosyl-cobalamin	Methylation, methylmalonyl mutase	Megaloblastic anaemia + SACD

High-yield: Of all B vitamins, only B12 has hepatic stores lasting years; folate stores last only ~3–4 months, which is why folate deficiency appears far sooner (e.g. in pregnancy, alcoholism, haemolysis).

B1 — Thiamine (TPP)

Coenzyme TPP participates in oxidative decarboxylation and transketolase reactions. Remember the four TPP-dependent enzymes:

1. Pyruvate dehydrogenase → links glycolysis to TCA
2. α-Ketoglutarate dehydrogenase → TCA cycle
3. Branched-chain α-keto acid dehydrogenase → BCAA catabolism (defect = Maple Syrup Urine Disease)
4. Transketolase → HMP shunt (the basis of the diagnostic test)

Mnemonic: "The dehydrogenases need TPP" — Pyruvate, α-KG, BCKA — plus transketolase.

Deficiency

• Dry beriberi → symmetrical peripheral neuropathy, wrist/foot drop, areflexia.
• Wet beriberi → high-output cardiac failure, peripheral vasodilation, oedema.
• Infantile beriberi → in breastfed infants of thiamine-deficient mothers; aphonia, cardiac failure.
• Wernicke encephalopathy → triad of ophthalmoplegia + ataxia + confusion (CONFusion, Ataxia, Nystagmus = "CAN't walk, CAN't see, CAN't think"). Reversible.
• Korsakoff psychosis → anterograde amnesia + confabulation; mammillary body damage; largely irreversible.

High-yield: In a suspected alcoholic, give thiamine BEFORE glucose. A glucose load consumes residual thiamine and can precipitate acute Wernicke encephalopathy.

Investigation of choice: Erythrocyte transketolase activity with TPP stimulation — a >25% rise after adding TPP confirms deficiency. Blood pyruvate and lactate are also raised.

B2 — Riboflavin (FMN, FAD)

Riboflavin yields FMN and FAD, the prosthetic groups of flavoproteins in redox reactions (e.g. succinate dehydrogenase, complex I/II of ETC, glutathione reductase, xanthine oxidase). Riboflavin is light-sensitive — neonatal phototherapy can cause deficiency.

Deficiency ("ariboflavinosis")

• Angular stomatitis / cheilosis (cracks at mouth angles)
• Glossitis (magenta tongue)
• Seborrhoeic dermatitis, corneal vascularisation
• Normochromic normocytic anaemia

Test: Erythrocyte glutathione reductase activity coefficient (EGRAC) — a ratio >1.4 indicates deficiency.

B3 — Niacin (NAD⁺/NADP⁺)

Niacin forms NAD⁺ and NADP⁺, the universal hydride acceptors in dehydrogenase reactions. Niacin can be synthesised endogenously from tryptophan (60 mg tryptophan → 1 mg niacin), a reaction requiring B6, B2 and iron.

Pellagra — the "3 Ds (4 Ds)"

Dermatitis → Diarrhoea → Dementia → Death

• Photosensitive dermatitis in sun-exposed areas: Casal's necklace (around the neck), gloves-and-boots distribution.
• Diarrhoea, glossitis, achlorhydria.
• Dementia, depression, irritability.

Causes of secondary pellagra:

• Hartnup disease — defective neutral amino-acid (tryptophan) transport in gut/kidney.
• Carcinoid syndrome — tryptophan diverted to serotonin synthesis.
• Isoniazid (INH) — depletes B6, reducing tryptophan→niacin conversion.

High-yield: Both Hartnup disease and carcinoid syndrome cause pellagra-like dermatitis because they limit tryptophan available for niacin synthesis.

Toxicity: Pharmacological niacin (used as a lipid-lowering agent) causes prostaglandin-mediated cutaneous flushing, blocked by aspirin pre-treatment; also hepatotoxicity and hyperuricaemia.

B5 — Pantothenic acid (Coenzyme A)

Component of Coenzyme A (CoA) and the acyl carrier protein (ACP) of fatty-acid synthase. Central to acyl transfer — pyruvate → acetyl-CoA, fatty-acid oxidation and synthesis, TCA cycle. Deficiency is rare (ubiquitous in diet — "pantothenic" = everywhere) and presents as burning feet syndrome and adrenal insufficiency.

B6 — Pyridoxine (PLP)

The active form pyridoxal phosphate (PLP) is the most versatile B-coenzyme, central to amino-acid metabolism:

• Transamination (all aminotransferases — ALT, AST)
• Decarboxylation → neurotransmitters (GABA, dopamine, serotonin, histamine)
• δ-Aminolevulinic acid (ALA) synthase → first/rate-limiting step of haem synthesis
• Glycogen phosphorylase cofactor
• Cystathionine synthesis (homocysteine metabolism)

Deficiency

• Sideroblastic anaemia (microcytic, hypochromic) from impaired haem synthesis — ringed sideroblasts in marrow.
• Peripheral neuropathy
• Convulsions in infants (reduced GABA)
• Hyperhomocysteinaemia, seborrhoeic dermatitis, glossitis

High-yield (most tested): Isoniazid (INH) binds and inactivates pyridoxine → peripheral neuropathy and seizures. Co-prescribe pyridoxine 10–25 mg/day, especially in slow acetylators, diabetics, alcoholics, and pregnancy. INH overdose seizures are treated with high-dose IV pyridoxine.

Other B6-depleting drugs: Penicillamine, cycloserine, hydralazine, oral contraceptives, levodopa (B6 accelerates peripheral conversion of L-dopa, reducing its efficacy — relevant when L-dopa is given without carbidopa).

Toxicity: Chronic high-dose pyridoxine itself causes a dose-dependent sensory (dorsal column) peripheral neuropathy — a rare example of B-vitamin toxicity.

B7 — Biotin

Prosthetic group (as carbocybiotin) for carboxylase enzymes — the body's CO₂ carriers:

1. Pyruvate carboxylase (gluconeogenesis)
2. Acetyl-CoA carboxylase (fatty-acid synthesis; rate-limiting)
3. Propionyl-CoA carboxylase (odd-chain FA / BCAA)
4. β-Methylcrotonyl-CoA carboxylase (leucine)

Mnemonic: "Biotin = CO₂ carrier for carboxylases (PAP-β)."

Deficiency

• Alopecia, periorificial dermatitis, conjunctivitis, lactic acidosis, hypotonia.
• Causes: prolonged raw egg white ingestion (avidin binds biotin), long-term antibiotics (kill gut flora), and inherited biotinidase deficiency (treatable inborn error, screened on newborn panels).

B9 — Folate (THF) & B12 — Cobalamin

These are paired because both cause megaloblastic anaemia through the methionine synthase / "folate trap" mechanism.

One-carbon metabolism — the linchpin

Methionine synthase converts homocysteine → methionine, requiring B12 (methylcobalamin) and using a methyl group from N⁵-methyl-THF, regenerating free THF for DNA synthesis (thymidylate synthesis).

The methyl-folate trap: In B12 deficiency, methionine synthase stalls → folate is trapped as N⁵-methyl-THF and cannot be recycled into the forms needed for purine/thymidine synthesis → functional folate deficiency → megaloblastic anaemia. This is why B12 deficiency anaemia partially responds to folate — but folate does not correct the neurological damage and can mask the anaemia.

High-yield: Never treat megaloblastic anaemia with folate alone until B12 deficiency is excluded — folate corrects the anaemia but allows subacute combined degeneration (SACD) to progress irreversibly.

B12 — Cobalamin

Two B12-dependent reactions in humans:

**Methylcobalamin → ** homocysteine + N⁵-methyl-THF → methionine + THF (methionine synthase). **Adenosylcobalamin → ** L-methylmalonyl-CoA → succinyl-CoA (methylmalonyl-CoA mutase). Blockade here causes accumulation of methylmalonic acid (MMA) and abnormal odd-chain/branched fatty acids incorporated into neuronal myelin → demyelination.

Absorption pathway (commonly asked): Dietary B12 (animal foods only) → freed by gastric acid/pepsin → binds R-protein (haptocorrin) in saliva → pancreatic proteases release it in duodenum → binds intrinsic factor (IF) from gastric parietal cells → absorbed at the terminal ileum via cubilin receptor → carried in blood by transcobalamin II.

Causes of B12 deficiency:

• Pernicious anaemia — autoimmune destruction of parietal cells; anti-IF and anti-parietal cell antibodies; associated atrophic gastritis, achlorhydria.
• Terminal ileal disease/resection (Crohn's), Diphyllobothrium latum (fish tapeworm), blind-loop bacterial overgrowth, strict vegans, metformin, chronic PPI, nitrous oxide abuse (oxidises cobalt).

Subacute combined degeneration (SACD): degeneration of dorsal columns (loss of vibration/proprioception, sensory ataxia, positive Romberg) + lateral corticospinal tracts (spasticity, upgoing plantars) + spinocerebellar tracts. Peripheral neuropathy and dementia may coexist.

Folate

• Sources: green leafy vegetables, liver, legumes (heat-labile).
• Absorbed in jejunum as monoglutamate.
• Deficiency causes megaloblastic anaemia and, critically, neural tube defects (NTDs) in the fetus.

High-yield: Periconceptional folic acid 400 µg/day (and 4–5 mg/day if previous NTD-affected pregnancy or on antiepileptics) prevents NTDs. Start before conception because the neural tube closes by day 28.

Drugs causing folate deficiency: Methotrexate (dihydrofolate reductase inhibitor), trimethoprim, phenytoin, sulfasalazine, alcohol.

B12 vs Folate deficiency — the discriminator table

Feature	B12 deficiency	Folate deficiency
Body stores	Years (liver)	Months
Serum methylmalonic acid (MMA)	Raised	Normal
Serum homocysteine	Raised	Raised
Neurological signs (SACD)	Present	Absent
Schilling test	Was abnormal	Normal
Classic cause	Pernicious anaemia, vegan	Pregnancy, alcoholism, MTX
Risk on giving folate alone	Worsens neuro disease	—

High-yield: Raised serum methylmalonic acid (MMA) is the single best discriminator — elevated in B12 deficiency but normal in folate deficiency (because the mutase reaction is B12-specific). Homocysteine is raised in both.

Peripheral smear (both): macro-ovalocytes, hypersegmented neutrophils (>5 lobes), pancytopenia in severe cases; raised LDH and indirect bilirubin (ineffective erythropoiesis). Bone marrow: megaloblasts, nuclear-cytoplasmic asynchrony.

Diagnostic / investigation of choice — quick map

• B1: Erythrocyte transketolase + TPP effect (>25% activation).
• B2: EGRAC >1.4.
• B3: Urinary N-methylnicotinamide (low).
• B6: Plasma PLP level.
• B9: Serum + RBC folate (RBC folate reflects tissue stores better).
• B12: Serum B12, then MMA + homocysteine if borderline; antibodies for pernicious anaemia. (Schilling test is historical.)

Management / drug of choice

• Wernicke encephalopathy: IV thiamine (high dose) before any glucose.
• Pellagra: oral niacinamide (nicotinamide, no flushing).
• INH neuropathy / overdose: pyridoxine.
• Pernicious anaemia: lifelong parenteral (IM) hydroxocobalamin/cyanocobalamin (oral fails — no IF).
• Megaloblastic anaemia of folate deficiency: oral folic acid 5 mg/day after excluding B12 deficiency.

Complications

• Untreated Wernicke → Korsakoff (irreversible amnesia).
• B12 deficiency SACD becomes irreversible after months; high-output failure in wet beriberi.
• Megaloblastic anaemia → cardiac failure, neutropenic sepsis.
• Folate deficiency in pregnancy → NTDs (anencephaly, spina bifida), abruption, IUGR.

Key differentials

• Megaloblastic vs non-megaloblastic macrocytosis: alcohol, liver disease, hypothyroidism, reticulocytosis, myelodysplasia (MDS) — no hypersegmented neutrophils, normal MMA/homocysteine.
• SACD vs MS / tabes dorsalis / Friedreich ataxia: check B12 and MMA; SACD spares pain/temperature early (dorsal column predominant).
• Sideroblastic anaemia: distinguish B6-responsive (hereditary, lead, alcohol) from iron-overload causes; ringed sideroblasts on Prussian blue.

Recently asked / exam angle

• Thiamine before glucose in alcoholics — repeated single-best-answer favourite.
• MMA raised in B12 but normal in folate deficiency — the discriminator MCQ.
• Isoniazid + pyridoxine interaction and L-dopa + B6 interaction.
• Methyl-folate trap mechanism explaining why folate masks B12 anaemia.
• TPP-dependent enzymes list, and transketolase as the test (also links to HMP shunt).
• Casal's necklace / Hartnup / carcinoid as causes of pellagra.
• B12 absorption sequence (R-binder → IF → terminal ileum → transcobalamin II) — order-matching questions.
• Avidin in raw egg white causing biotin deficiency.
• Newer image-based items on hypersegmented neutrophils and ringed sideroblasts.

Rapid revision

1. Only B12 and B6 have meaningful toxicity; B6 toxicity = sensory neuropathy.
2. B12 stores last years; folate stores last months.
3. TPP enzymes: pyruvate DH, α-KG DH, branched-chain keto-acid DH, transketolase.
4. Wernicke triad = ophthalmoplegia + ataxia + confusion; give thiamine before glucose.
5. Pellagra = dermatitis, diarrhoea, dementia (3 Ds); Casal's necklace; tryptophan→niacin needs B6.
6. B6/PLP = transamination + ALA synthase; INH depletes it → neuropathy.
7. Biotin = carboxylases; raw egg white avidin causes deficiency.
8. B12 reactions: methionine synthase (methyl-B12) + methylmalonyl-CoA mutase (adenosyl-B12).
9. Methyl-folate trap explains functional folate deficiency in B12 deficiency.
10. Raised MMA = B12 deficiency; homocysteine raised in both B12 and folate.
11. Never give folate alone in megaloblastic anaemia until B12 excluded (risk of SACD).
12. Folic acid 400 µg periconceptional (4–5 mg if prior NTD/on AEDs) prevents NTDs.