Foundational Science Series

Core Topics: Vitamins & Minerals

High-yield reference for water-soluble vitamins, fat-soluble vitamins, and trace minerals — mapped to USMLE Step 1/2 CK foundational science objectives with clinical correlations.

How to Use This Resource

Each vitamin/mineral section includes: Active Forms, Key Functions (enzyme cofactors), Deficiency Syndromes, and High-Yield Facts (clinical pearls, drug interactions). Use for active recall, spaced repetition, and integration with clinical cases.

Water-Soluble Vitamins (B-Complex & C)

Essential cofactors for metabolism, neurotransmission, and antioxidant defense

Vitamin B1 (Thiamine)
  • Active Form: Thiamine pyrophosphate (TPP)
  • Functions: Cofactor for decarboxylation reactions:
    • Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
    • α-Ketoglutarate dehydrogenase (TCA cycle)
    • Branched-chain α-ketoacid dehydrogenase (BCAA metabolism)
    • Transketolase (pentose phosphate pathway)
  • Deficiency: Beriberi (Wet: high-output HF, edema; Dry: peripheral neuropathy); Wernicke-Korsakoff (confusion, ataxia, ophthalmoplegia, confabulation)
  • Clinical Pearl: Give thiamine BEFORE glucose in alcoholics to prevent precipitating Wernicke's
Vitamin B2 (Riboflavin)
  • Active Forms: FAD, FMN
  • Functions: Electron carrier in redox reactions (Succinate dehydrogenase, fatty acid oxidation, dihydroorotate dehydrogenase)
  • Deficiency: Cheilosis (angular stomatitis), glossitis, corneal vascularization
  • Mnemonic: "2 C's" = Cheilosis, Corneal vascularization
Vitamin B3 (Niacin)
  • Active Forms: NAD⁺, NADP⁺
  • Functions: Redox reactions (glycolysis, TCA, ETC); NADPH for fatty acid synthesis
  • Synthesis: From tryptophan (requires B6, B2, iron)
  • Deficiency: Pellagra (3 D's: Dermatitis [Casal necklace], Diarrhea, Dementia → Death)
  • Causes: Corn diet, Hartnup disease, carcinoid syndrome, isoniazid
  • Pharmacology: Dyslipidemia (↓VLDL, ↑HDL); Side effects: flushing, hyperglycemia, hyperuricemia
Vitamin B5 (Pantothenic Acid)
  • Active Form: Coenzyme A (CoA)
  • Functions: Acyl group carrier (fatty acid synthesis/oxidation, TCA, cholesterol synthesis)
  • Deficiency: Rare ("pantothen" = everywhere); dermatitis, enteritis, alopecia, adrenal insufficiency, "burning feet syndrome"
Vitamin B6 (Pyridoxine)
  • Active Form: Pyridoxal phosphate (PLP)
  • Functions: Transamination (ALT/AST), decarboxylation, glycogen phosphorylase, heme synthesis (ALA synthase), neurotransmitter synthesis (serotonin, dopamine, GABA), cystathionine β-synthase
  • Deficiency: Peripheral neuropathy, sideroblastic anemia, seizures (↓GABA)
  • Causes: Isoniazid (forms hydrazone with PLP), oral contraceptives
  • Toxicity: Sensory neuropathy (high doses)
Vitamin B7 (Biotin)
  • Functions: Cofactor for carboxylation reactions (CO₂ carrier)
  • Enzymes: Pyruvate carboxylase, Acetyl-CoA carboxylase, Propionyl-CoA carboxylase
  • Mnemonic: "Biotin is for Carboxylases" (PAP: Pyruvate, Acetyl-CoA, Propionyl-CoA)
  • Deficiency: Dermatitis, alopecia, enteritis
  • Causes: Raw egg whites (avidin binds biotin), antibiotic use (kills gut flora)
Vitamin B9 (Folate)
  • Active Form: Tetrahydrofolate (THF)
  • Functions: One-carbon transfer for purine synthesis, thymidylate synthesis (dUMP→dTMP), methionine synthesis
  • Deficiency: Megaloblastic anemia, neural tube defects (spina bifida, anencephaly); NO neurologic symptoms
  • Causes: Alcoholism, pregnancy, methotrexate, phenytoin, trimethoprim
  • Supplementation: 400 μg/day preconception/pregnancy
Vitamin B12 (Cobalamin)
  • Functions: Cofactor for methionine synthase (homocysteine→methionine) and methylmalonyl-CoA mutase (methylmalonyl-CoA→succinyl-CoA)
  • Deficiency: Megaloblastic anemia + neurologic symptoms (subacute combined degeneration: dorsal columns/corticospinal tracts)
  • Labs: ↑Methylmalonic acid (MMA), ↑homocysteine
  • Causes: Pernicious anemia, gastrectomy, ileal resection, vegan diet, Diphyllobothrium latum
  • Absorption: Requires intrinsic factor (parietal cells), terminal ileum; liver stores (3-5 years)
  • Pearl: Correct B12 before folate to avoid masking neurologic damage
Vitamin C (Ascorbic Acid)
  • Functions: Antioxidant, collagen synthesis (hydroxylation of proline/lysine), iron absorption (Fe³⁺→Fe²⁺), dopamine β-hydroxylase
  • Deficiency: Scurvy (swollen gums, bleeding, poor wound healing, petechiae, corkscrew hairs, easy bruising)
  • Toxicity: Nausea, diarrhea, calcium oxalate kidney stones
  • At-Risk: Elderly, alcoholics, smokers (↑requirement)
High-Yield: Water-Soluble Vitamins
Wernicke-Korsakoff
Acute: Wernicke (confusion, ataxia, ophthalmoplegia); Chronic: Korsakoff (confabulation, amnesia); give thiamine BEFORE glucose
Pellagra Triad
3 D's: Dermatitis (photosensitive/Casal necklace), Diarrhea, Dementia; caused by niacin deficiency or Hartnup/carcinoid/isoniazid
B12 vs Folate
Both cause megaloblastic anemia; only B12 causes neurologic symptoms (subacute combined degeneration) and ↑MMA
Isoniazid Toxicity
Depletes B6 (pyridoxine) → peripheral neuropathy, sideroblastic anemia, seizures; supplement B6 with INH therapy

Fat-Soluble Vitamins (A, D, E, K)

Stored in liver/adipose; risk of toxicity; require bile for absorption

Vitamin A (Retinol)
  • Forms: Retinol (storage), retinal (vision), retinoic acid (gene expression)
  • Functions: Vision (rhodopsin/night vision), epithelial maintenance, immune function, growth
  • Deficiency: Night blindness (nyctalopia), xerophthalmia (Bitot spots, keratomalacia), squamous metaplasia, immune dysfunction
  • Toxicity: Acute (nausea, vertigo); Chronic (alopecia, dry skin, hepatotoxicity, pseudotumor cerebri); Teratogenic (isotretinoin)
  • Sources: Liver, fish, dairy; β-carotene (orange/yellow veggies)
Vitamin D (Cholecalciferol)
  • Activation: Skin (7-dehydrocholesterol → D3 via UV) → Liver (25-OH-D) → Kidney (1,25-(OH)₂-D [active])
  • Functions: ↑Intestinal Ca²⁺/PO₄ absorption, ↑bone resorption (with PTH), ↑renal Ca²⁺ reabsorption
  • Deficiency: Rickets (children: bowing, rachitic rosary), Osteomalacia (adults: bone pain, fractures)
  • Labs: ↓Ca²⁺, ↓PO₄, ↑PTH, ↑ALP
  • Toxicity: Hypercalcemia, hypercalciuria, metastatic calcification, kidney stones
Vitamin E (Tocopherol)
  • Functions: Antioxidant (protects RBCs/membranes from lipid peroxidation)
  • Deficiency: Hemolytic anemia (premies), spinocerebellar ataxia, peripheral neuropathy (mimics B12), retinopathy
  • Causes: Fat malabsorption (cystic fibrosis, abetalipoproteinemia)
  • Toxicity: Rare; may enhance warfarin anticoagulation
Vitamin K (Phylloquinone)
  • Forms: K1 (plants), K2 (gut bacteria), K3 (synthetic)
  • Functions: γ-carboxylation of clotting factors II, VII, IX, X and proteins C/S; bone metabolism (osteocalcin)
  • Deficiency: Bleeding diathesis (↑PT/INR, ↑PTT late), hemorrhagic disease of newborn
  • Causes: Fat malabsorption, antibiotics (↓gut flora), warfarin (antagonist)
  • Reversal: Vitamin K (slow), FFP/PCC (rapid)
High-Yield: Fat-Soluble Vitamins
Absorption Requirement
All fat-soluble vitamins require bile acids for absorption; deficiency seen in cystic fibrosis, biliary obstruction, celiac disease
Vitamin A Toxicity
Teratogenic (cleft palate, cardiac defects); isotretinoin contraindicated in pregnancy; chronic toxicity → pseudotumor cerebri
Vitamin D Activation
Kidney 1α-hydroxylase stimulated by PTH; inhibited by FGF23; measured level is 25-OH-D
Warfarin Mechanism
Inhibits vitamin K epoxide reductase → ↓γ-carboxylation of factors II, VII, IX, X, Protein C/S; monitored by PT/INR

Trace Minerals

Essential cofactors for enzymes, structural proteins, and metabolic regulation

Zinc

  • Functions: Cofactor for 100+ enzymes (carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase), wound healing, immune function (T-cells), taste/smell, zinc finger transcription factors
  • Deficiency: Acrodermatitis enteropathica (perioral/acral dermatitis, diarrhea, alopecia), delayed wound healing, hypogonadism, dysgeusia
  • Causes: Malabsorption, alcoholism, TPN without supplementation

Copper

  • Functions: Cofactor for cytochrome c oxidase, lysyl oxidase (collagen cross-linking), ceruloplasmin (Fe²⁺→Fe³⁺), dopamine β-hydroxylase, SOD
  • Deficiency: Microcytic anemia, neutropenia, osteoporosis, Menkes disease (X-linked: kinky hair, neurodegeneration)
  • Toxicity: Wilson disease (AR: copper accumulation → hepatitis, cirrhosis, Kayser-Fleischer rings, neuropsychiatric symptoms); treat with penicillamine, trientine, zinc

Iron

  • Functions: Heme synthesis (Hb, myoglobin, cytochromes), electron transport, oxygen transport
  • Deficiency: Microcytic hypochromic anemia, koilonychia (spoon nails), pica, glossitis, angular cheilitis; Labs: ↓Fe, ↓ferritin, ↑TIBC, ↓saturation
  • Toxicity: Acute (GI hemorrhage, shock); Chronic (hemochromatosis: cirrhosis, diabetes, cardiomyopathy, bronzing, arthritis); treat with deferoxamine (acute), phlebotomy (chronic)

Selenium

  • Functions: Cofactor for glutathione peroxidase (antioxidant), thyroid hormone metabolism (deiodinases)
  • Deficiency: Keshan disease (cardiomyopathy), muscle weakness, nail changes
  • Toxicity: Garlic breath, hair loss, nail changes, neurologic symptoms

Chromium

  • Functions: Enhances insulin action (glucose tolerance factor)
  • Deficiency: Impaired glucose tolerance, peripheral neuropathy

Manganese

  • Functions: Cofactor for SOD, arginase, pyruvate carboxylase
  • Toxicity: Parkinson-like symptoms (manganism) in miners/welders

Iodine

  • Functions: Thyroid hormone synthesis (T3, T4)
  • Deficiency: Goiter, cretinism (congenital hypothyroidism: ID, short stature, coarse features), hypothyroidism
  • Toxicity: Thyroiditis, hyper/hypothyroidism (Wolff-Chaikoff effect)

Fluoride

  • Functions: Strengthens enamel (fluorapatite), prevents dental caries
  • Deficiency: Dental caries
  • Toxicity: Fluorosis (mottled enamel), osteosclerosis
High-Yield: Trace Minerals
Zinc Deficiency
Acrodermatitis enteropathica: Perioral/acral dermatitis, diarrhea, alopecia; also causes hypogonadism and dysgeusia (loss of taste)
Copper Disorders
Menkes: X-linked, kinky hair, neurodegeneration (ATP7A defect); Wilson: AR, Kayser-Fleischer rings, hepatitis (ATP7B defect)
Iron Studies
Deficiency: ↓Ferritin, ↑TIBC, ↓Saturation; Hemochromatosis: ↑Ferritin, ↓TIBC, ↑Saturation; Anemia of Chronic Disease: ↑Ferritin, ↓TIBC
Selenium & Thyroid
Selenium is cofactor for deiodinases (T4→T3 conversion); deficiency linked to Keshan cardiomyopathy
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Evidence & Further Reading