Vitamins & Micronutrients — USMLE Step 1 Notes

Overview: water- vs fat-soluble

• Water-soluble (B-complex and C): not stored (except B12), so deficiency appears relatively quickly; excess is usually excreted. Most act as enzyme cofactors.
• Fat-soluble (A, D, E, K): absorbed with dietary fat and stored in liver/fat, so they accumulate and can be toxic; fat malabsorption (cystic fibrosis, cholestasis, coeliac) causes combined A, D, E, K deficiency.

Vitamin B1 — thiamine

• Role: cofactor (as thiamine pyrophosphate) for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase and branched-chain ketoacid dehydrogenase — central to glucose metabolism.
• Source: whole grains, pork, legumes.
• Deficiency: beriberi — dry (symmetrical peripheral neuropathy) and wet (high-output cardiac failure/oedema); and Wernicke-Korsakoff in alcohol excess (confusion, ophthalmoplegia, ataxia; then amnesia/confabulation). Give thiamine BEFORE glucose.

Vitamin B2 — riboflavin

• Role: precursor of FAD and FMN (redox cofactors in the electron transport chain and many dehydrogenases).
• Source: dairy, eggs, green vegetables.
• Deficiency: cheilosis, angular stomatitis, glossitis, seborrhoeic dermatitis and corneal neovascularisation (the '2 C's': cheilosis and corneal vascularisation).

Vitamin B3 — niacin

• Role: precursor of NAD+ and NADP+ (redox reactions); can be made from tryptophan (needs B6).
• Source: meat, fish, grains.
• Deficiency: pellagra — the 3 D's: Dermatitis (photosensitive, 'Casal necklace'), Diarrhoea and Dementia (a 4th D = Death if untreated). Seen with maize-based diets, Hartnup disease and carcinoid syndrome (tryptophan diverted), and isoniazid.
• Excess: facial flushing (prostaglandin-mediated) and hyperglycaemia/hyperuricaemia when used for dyslipidaemia.

Vitamin B5 — pantothenic acid

• Role: a component of coenzyme A and fatty-acid synthase — essential for acyl transfer in fatty-acid and energy metabolism.
• Source: widespread in foods (pantothen = 'from everywhere').
• Deficiency: rare — dermatitis, enteritis, alopecia, adrenal insufficiency and 'burning feet' (paraesthesia).

Vitamin B6 — pyridoxine

• Role: cofactor (pyridoxal phosphate) for transamination and decarboxylation, haem synthesis (ALA synthase), glycogen phosphorylase, and synthesis of neurotransmitters (GABA, serotonin, dopamine) and niacin.
• Source: meat, vegetables, nuts.
• Deficiency: sideroblastic anaemia, peripheral neuropathy (classically with isoniazid — co-prescribe B6), cheilosis/glossitis and, in infants, convulsions.
• Excess: a dose-dependent sensory peripheral neuropathy.

Vitamin B7 — biotin

• Role: cofactor for carboxylases — pyruvate carboxylase, acetyl-CoA carboxylase and propionyl-CoA carboxylase.
• Source: widespread; synthesised by gut bacteria.
• Deficiency: rare — dermatitis, alopecia and enteritis; caused by excess raw egg whites (avidin binds biotin) or prolonged antibiotics.

Vitamin B9 — folate

• Role: as tetrahydrofolate, carries one-carbon units for DNA/purine and methionine synthesis; essential for rapidly dividing cells.
• Source: leafy green vegetables (folium = leaf); stores last only a few months.
• Deficiency: megaloblastic anaemia WITHOUT neurological signs; neural tube defects (supplement periconceptionally). Causes: poor diet, alcohol, pregnancy, and drugs (methotrexate, trimethoprim, phenytoin).

Vitamin B12 — cobalamin

• Role: cofactor for methionine synthase (folate/methylation) and methylmalonyl-CoA mutase (odd-chain fatty acids/myelin).
• Source: animal products only (meat, eggs, dairy); large hepatic stores last years.
• Deficiency: megaloblastic anaemia WITH neurological signs — subacute combined degeneration of the cord (dorsal columns and corticospinal tracts). Raised methylmalonic acid. Causes: pernicious anaemia (loss of intrinsic factor), terminal ileal disease/resection, and vegan diets. Treat B12 before/with folate to protect the cord.

Vitamin C — ascorbic acid

• Role: hydroxylation of proline/lysine in collagen synthesis, an antioxidant, aids iron absorption (reduces Fe3+ to Fe2+) and is a cofactor for dopamine beta-hydroxylase.
• Source: citrus fruit, peppers, green vegetables.
• Deficiency: scurvy — swollen bleeding gums, perifollicular haemorrhages, 'corkscrew' hairs, poor wound healing, easy bruising and anaemia.
• Excess: can promote calcium-oxalate renal stones.

Vitamin A — retinol

• Role: vision (retinal is part of rhodopsin), epithelial cell differentiation, immune function and growth; used therapeutically in acute promyelocytic leukaemia (ATRA) and measles.
• Source: liver, fish, dairy; provitamin carotenoids in orange/leafy vegetables.
• Deficiency: night blindness, dry eyes (xerophthalmia), Bitot spots, keratomalacia, follicular hyperkeratosis and impaired immunity.
• Excess: teratogenic (isotretinoin — pregnancy contraindication), raised intracranial pressure, hepatotoxicity, dry skin and bone/joint pain.

Vitamin D

• Role: raises calcium and phosphate absorption from the gut and supports bone mineralisation; activated in the skin (with UV), then hydroxylated in the liver (25-OH) and kidney (1,25-dihydroxy, the active form).
• Source: sunlight-driven skin synthesis, oily fish, fortified foods.
• Deficiency: rickets in children (bowing, widened growth plates) and osteomalacia in adults (bone pain, proximal weakness); low calcium/phosphate with high ALP and PTH.
• Excess: hypercalcaemia (stones, constipation, confusion).

Vitamin E — tocopherol

• Role: a lipid antioxidant protecting cell membranes (and red cells) from oxidative damage.
• Source: vegetable oils, nuts, seeds.
• Deficiency: rare — haemolytic anaemia and neuromuscular disease (ataxia, peripheral neuropathy, loss of proprioception); seen in fat malabsorption.
• Excess: can antagonise vitamin K and increase bleeding.

Vitamin K

• Role: cofactor for gamma-carboxylation of clotting factors II, VII, IX, X and proteins C and S (the '1972' factors).
• Source: green leafy vegetables and synthesis by gut bacteria.
• Deficiency: bleeding with a raised PT/INR; classically haemorrhagic disease of the newborn (sterile gut, low stores) — prevented by IM vitamin K at birth; also in malabsorption, prolonged antibiotics and warfarin therapy (which blocks vitamin K epoxide reductase).

High-yield revision notes; verify against a primary source before clinical use.