water-soluble vitamins

**Classification** - B-complex: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), B12 (cobalamin). - Vitamin C (ascorbic acid).

**General features** - Absorbed in the small intestine. Most absorption is by carrier-mediated transport. B12 needs intrinsic factor and is absorbed in the terminal ileum. Folate is absorbed in the jejunum. - Not stored in significant amounts, so they must be replenished regularly. Exception: B12 is stored in the liver for 3-5 years. Folate stores last about 3-4 months. - Excess is excreted in urine, so toxicity is uncommon. Notable exceptions: niacin (flushing from prostaglandins, hepatotoxicity, hyperglycemia, hyperuricemia), B6 (sensory peripheral neuropathy), and vitamin C (oxalate kidney stones). - Alcohol use disorder, malnutrition, malabsorption, and dialysis are common causes of multiple deficiencies.

**High-yield by vitamin** - **B1 (thiamine)**: Cofactor (as TPP) for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, and transketolase (HMP shunt). Deficiency causes beriberi (dry: polyneuropathy. Wet: high-output heart failure) and Wernicke-Korsakoff syndrome (confusion, ophthalmoplegia, ataxia, then confabulation and amnesia). Give thiamine before glucose in at-risk patients. Diagnose by elevated RBC transketolase activity after thiamine. - **B2 (riboflavin)**: FAD and FMN cofactors. Deficiency causes the "2 C's and 2 S's": cheilosis, corneal vascularization, stomatitis, and sore throat (glossitis). - **B3 (niacin)**: NAD+/NADP+. Made from tryptophan, which needs B6. Deficiency causes pellagra (the 4 D's: diarrhea, dermatitis, dementia, death). Causes include Hartnup disease, carcinoid syndrome, and isoniazid. Used therapeutically to raise HDL and lower LDL and TG. Side effect is flushing, which is reduced by aspirin pretreatment. - **B5 (pantothenic acid)**: Component of CoA and the fatty acid synthase acyl carrier protein. Deficiency is rare (burning feet, adrenal insufficiency-like symptoms). - **B6 (pyridoxine)**: Active form is PLP. Used in transamination, decarboxylation (e.g., synthesis of dopamine, serotonin, GABA, and heme via ALA synthase), and glycogen phosphorylase. Deficiency causes sideroblastic anemia, cheilosis, glossitis, peripheral neuropathy, and seizures. It is induced by isoniazid, so give B6 with INH. - **B7 (biotin)**: Cofactor for carboxylases (pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase). Deficiency causes dermatitis, alopecia, and enteritis. Causes include raw egg white (avidin) consumption and long-term antibiotic use. - **B9 (folate)**: Active form is tetrahydrofolate (THF), needed for one-carbon transfer and purine/thymidine synthesis. Deficiency causes megaloblastic anemia with hypersegmented neutrophils, elevated homocysteine, and normal methylmalonic acid. It is not neurologic. Neural tube defects occur in pregnancy. Causes include phenytoin, methotrexate, and trimethoprim. Supplement before conception. - **B12 (cobalamin)**: Cofactor for homocysteine methyltransferase (homocysteine to methionine) and methylmalonyl-CoA mutase. Deficiency causes megaloblastic anemia plus subacute combined degeneration (dorsal columns and lateral corticospinal tracts). Both homocysteine and methylmalonic acid are elevated. Causes include pernicious anemia (anti-intrinsic factor or anti-parietal cell antibodies), terminal ileum disease (Crohn disease), *Diphyllobothrium latum*, gastrectomy, and strict veganism. Treat with IM or high-dose oral B12. Giving folate alone can correct the anemia but not the neurologic damage. - **Vitamin C (ascorbic acid)**: Needed for hydroxylation of proline and lysine in collagen synthesis. It also aids iron absorption (Fe3+ to Fe2+), serves as an antioxidant, and is a cofactor for dopamine β-hydroxylase. Deficiency causes scurvy (swollen gums, easy bruising, perifollicular hemorrhages, corkscrew hairs, poor wound healing, and subperiosteal hemorrhage). Excess causes oxalate nephrolithiasis and iron overload in susceptible patients.

**Contrast with fat-soluble vitamins (A, D, E, K)**: These are stored in fat and the liver, need bile salts and micelles for absorption, and are more likely to cause toxicity. Deficiency occurs in fat malabsorption states (cystic fibrosis, celiac disease, cholestasis, orlistat use).

**Test-taking pearls** - Alcoholic patient with confusion, ataxia, and ophthalmoplegia: thiamine. - Megaloblastic anemia plus neurologic findings: B12. Elevated MMA distinguishes B12 from folate deficiency. - TB patient on INH with neuropathy: B6. - Diarrhea, dermatitis, and dementia: niacin. - Bleeding gums and perifollicular hemorrhages: vitamin C.