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Uses of all vitamins and minerals

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Vitamins and Minerals: Uses, Functions, and Deficiency States

Sources: Harrison's Principles of Internal Medicine 22E, Robbins & Kumar Basic Pathology, Basic Medical Biochemistry 6e, Fischer's Mastery of Surgery 8e, Yamada's Textbook of Gastroenterology 7e

PART 1: VITAMINS

There are 13 essential vitamins - 4 fat-soluble and 9 water-soluble. They function as enzyme cofactors, antioxidants, hormonal precursors, and structural components. - Fischer's Mastery of Surgery 8e, p. 246

FAT-SOLUBLE VITAMINS (A, D, E, K)

Absorbed with dietary fat via chylomicrons. Poorly absorbed without bile or pancreatic enzymes. Stored in the liver and adipose tissue, so deficiency develops slowly but toxicity can accumulate.

VITAMIN A (Retinol / Retinoids)

Functions:
  • Vision - forms rhodopsin (rod cell pigment) for low-light vision and iodopsins (cone pigments) for color vision. This is why night blindness is the earliest sign of deficiency.
  • Epithelial differentiation - regulates orderly differentiation of mucus-secreting columnar epithelium. Deficiency causes squamous metaplasia and keratinization of mucous membranes.
  • Immune function - supports innate immunity; deficiency increases susceptibility to infections.
  • Reproduction and growth - retinoic acid regulates gene transcription via RAR/RXR nuclear receptors.
  • Antioxidant (as beta-carotene)
Sources: Liver, fish, eggs, milk, butter. Yellow/green vegetables (beta-carotene as provitamin A).
Deficiency:
  • Night blindness (nyctalopia) - earliest sign
  • Bitot spots and xerophthalmia (dry, keratinized conjunctiva)
  • Keratomalacia (corneal ulceration/blindness)
  • Follicular hyperkeratosis of skin
  • Increased susceptibility to infections
Toxicity (hypervitaminosis A): Headache, peeling skin, liver damage, teratogenicity. - Robbins & Kumar Basic Pathology, p. 292-295

VITAMIN D (Calciferol)

Functions:
  • Calcium and phosphorus homeostasis - active form 1,25-(OH)2-D (calcitriol) increases intestinal absorption of calcium and phosphorus.
  • Bone mineralization - required for calcium deposition in osteoid matrix.
  • PTH regulation - calcitriol suppresses PTH gene transcription.
  • Immune modulation - vitamin D receptors on immune cells modulate inflammatory responses.
  • Cell differentiation - anti-proliferative effects in certain tissues.
Sources: Fatty fish, fortified milk, sunlight (UV-B converts 7-dehydrocholesterol in skin to vitamin D3).
Deficiency:
  • Rickets in children - inadequate provisional calcification of epiphyseal cartilage; bowing of legs, rachitic rosary, craniotabes, delayed fontanelle closure.
  • Osteomalacia in adults - unmineralized bone matrix; bone pain, muscle weakness, stress fractures.
  • Secondary hyperparathyroidism - hypocalcemia triggers PTH secretion, causing phosphaturia. - Robbins & Kumar Basic Pathology, p. 295-299

VITAMIN E (Tocopherol)

Functions:
  • Primary antioxidant - protects cell membranes from lipid peroxidation by free radicals.
  • Protects polyunsaturated fatty acids in membranes, especially in RBCs and neurons.
  • Supports immune function.
Sources: Vegetable oils, nuts, seeds, leafy greens.
Deficiency:
  • Rare in adults; occurs mainly in fat malabsorption syndromes or abetalipoproteinemia.
  • Hemolytic anemia (fragile RBCs due to membrane oxidation)
  • Spinocerebellar ataxia and peripheral neuropathy
  • Ophthalmoplegia, pigmented retinopathy
  • Acanthocytosis

VITAMIN K (Phylloquinone / Menaquinone)

Functions:
  • Coagulation - essential cofactor for gamma-carboxylation of clotting factors II (prothrombin), VII, IX, and X, as well as anticoagulant proteins C and S.
  • Bone metabolism - carboxylates osteocalcin and matrix Gla protein, required for bone mineralization.
Sources: Green leafy vegetables (K1), gut bacteria synthesize K2. Newborns lack gut flora, hence prophylactic vitamin K injection at birth.
Deficiency:
  • Bleeding diathesis - prolonged PT and PTT
  • Hemorrhagic disease of the newborn
  • Risk increased by: warfarin use, fat malabsorption, broad-spectrum antibiotics (kill gut flora)

WATER-SOLUBLE VITAMINS (B complex + C)

Easily absorbed, not stored in significant quantities, so deficiency can develop within weeks on a deficient diet. Hemodialysis and diuretics deplete them. - Harrison's Principles of Internal Medicine 22E

VITAMIN C (Ascorbic Acid)

Functions:
  • Collagen synthesis - essential for hydroxylation of proline and lysine residues in procollagen. Without this, collagen triple helix is unstable.
  • Antioxidant - scavenges free radicals; regenerates vitamin E.
  • Iron absorption - reduces Fe3+ to Fe2+ in the gut, enhancing non-heme iron absorption.
  • Immune function - supports neutrophil function and wound healing.
  • Biosynthesis - required for synthesis of carnitine, norepinephrine, and bile acids.
Sources: Citrus fruits, strawberries, broccoli, bell peppers, potatoes.
Deficiency - Scurvy:
  • Perifollicular hemorrhages, corkscrew hairs
  • Bleeding gums (gingivitis), loose teeth
  • Poor wound healing
  • Subperiosteal hemorrhages (very painful in children)
  • Fatigue and anemia
  • Daily intake <10 mg/day for weeks leads to scurvy. - Basic Medical Biochemistry 6e

THIAMINE (Vitamin B1)

Functions:
  • Coenzyme (thiamine pyrophosphate) for decarboxylation of alpha-ketoacids: pyruvate to acetyl-CoA, alpha-ketoglutarate to succinyl-CoA.
  • Transketolase reaction in the pentose phosphate pathway.
  • Essential for energy generation, especially in glucose-dependent tissues (brain, heart).
Sources: Yeast, organ meats, pork, legumes, whole grains. Milled/polished rice is very low in thiamine.
Deficiency - Beriberi:
  • Wet beriberi: high-output cardiac failure, cardiomegaly, peripheral edema.
  • Dry beriberi: peripheral neuropathy, muscle weakness and wasting.
  • Wernicke-Korsakoff syndrome (in alcoholism): ophthalmoplegia, ataxia, confusion (Wernicke); anterograde amnesia and confabulation (Korsakoff). - Harrison's Principles of Internal Medicine 22E, p. 2149

RIBOFLAVIN (Vitamin B2)

Functions:
  • Precursor to FAD and FMN - coenzymes in the electron transport chain and oxidation-reduction reactions throughout metabolism.
  • Required for fatty acid beta-oxidation and amino acid catabolism.
Sources: Dairy products, meat, poultry, fish, fortified cereals.
Deficiency - Ariboflavinosis:
  • Cheilosis (cracking at corners of mouth), angular stomatitis
  • Glossitis (magenta tongue)
  • Seborrheic dermatitis
  • Photophobia, corneal vascularization
  • Normochromic normocytic anemia

NIACIN (Vitamin B3)

Functions:
  • Precursor to NAD+ and NADP+ - critical coenzymes in over 400 enzymatic reactions, especially energy metabolism (glycolysis, TCA cycle, oxidative phosphorylation).
  • In pharmacologic doses (1-3 g/day): raises HDL, lowers triglycerides and LDL (used for dyslipidemia).
Sources: Meat, poultry, fish, whole grains. Also synthesized from tryptophan (60 mg tryptophan = 1 mg niacin equivalent).
Deficiency - Pellagra (the "4 Ds"):
  • Dermatitis - photosensitive, pigmented rash on sun-exposed skin (Casal necklace)
  • Diarrhea
  • Dementia/Cognitive changes
  • Death (if untreated)
  • Seen in maize-based diets (corn is low in bioavailable niacin), alcoholism, carcinoid syndrome.

VITAMIN B6 (Pyridoxine)

Functions:
  • Coenzyme for >100 enzymatic reactions, especially amino acid metabolism (transamination, decarboxylation).
  • Required for synthesis of neurotransmitters: serotonin, dopamine, GABA, norepinephrine.
  • Required for synthesis of heme (aminolevulinic acid synthase reaction).
  • Involved in gluconeogenesis and glycogenolysis.
Sources: Meat, poultry, fish, eggs, fortified cereals, nuts, bananas.
Deficiency:
  • Seborrheic dermatitis, glossitis, cheilosis
  • Microcytic sideroblastic anemia (impaired heme synthesis)
  • Peripheral neuropathy
  • Epileptiform seizures (especially in infants)
  • Depression and confusion
  • Isoniazid (TB treatment) is a classic cause - it inhibits pyridoxine metabolism.

FOLATE (Vitamin B9)

Functions:
  • As tetrahydrofolate (THF): accepts and donates one-carbon units in biosynthesis of purines and thymidylate (DNA building blocks).
  • Essential for cell division and DNA synthesis.
  • Required for methionine synthesis (with B12) and homocysteine metabolism.
  • Critical in early pregnancy for neural tube closure.
Sources: Leafy green vegetables, citrus fruits, legumes, fortified cereals and breads.
Deficiency:
  • Megaloblastic anemia (impaired RBC maturation due to defective DNA synthesis)
  • Neural tube defects (spina bifida, anencephaly) - deficiency in first 4 weeks of pregnancy
  • Hyperhomocysteinemia (cardiovascular risk factor)
  • Stores deplete within weeks; common in alcoholism and pregnancy.

VITAMIN B12 (Cobalamin)

Functions:
  • Required for methionine synthase (converts homocysteine to methionine, regenerating THF for folate cycle).
  • Required for methylmalonyl-CoA mutase (odd-chain fatty acid metabolism, important in myelin synthesis).
  • DNA synthesis and RBC maturation.
Sources: Exclusively animal products (meat, fish, eggs, dairy). Strict vegans are at risk.
Deficiency:
  • Megaloblastic (macrocytic) anemia
  • Subacute combined degeneration of the spinal cord - degeneration of dorsal and lateral columns; paresthesias, ataxia, spasticity. This is unique to B12 (not folate) deficiency.
  • Glossitis, neuropsychiatric symptoms
  • Caused by: pernicious anemia (anti-intrinsic factor antibodies), gastrectomy, ileal disease (Crohn's), strict vegan diet, metformin use (reduces IF secretion).
  • Body stores last 1-2 years (large hepatic reserves).

BIOTIN (Vitamin B7)

Functions:
  • Coenzyme for carboxylase enzymes: acetyl-CoA carboxylase (fatty acid synthesis), pyruvate carboxylase (gluconeogenesis), propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase.
Sources: Liver, egg yolk, nuts, legumes. Also synthesized by gut bacteria.
Deficiency (rare):
  • Alopecia, dry scaly dermatitis
  • Conjunctivitis, glossitis
  • CNS abnormalities (lethargy, depression, hallucinations in severe cases)
  • Raw egg whites contain avidin, which binds biotin and prevents absorption.

PANTOTHENIC ACID (Vitamin B5)

Functions:
  • Component of Coenzyme A (CoA) - central to energy metabolism (acetyl-CoA in TCA cycle), fatty acid synthesis and oxidation, synthesis of steroid hormones, neurotransmitters, and phospholipids.
Sources: Widespread in food ("pantothenic" = from the Greek for "everywhere"). Meat, legumes, whole grains, vegetables.
Deficiency: Extremely rare under normal conditions. Experimental deficiency causes the "burning feet syndrome" (paresthesias in the feet), fatigue, and GI symptoms.

PART 2: ESSENTIAL MINERALS

Minerals are classified by daily requirement:
  • Macrominerals (>100 mg/day): Calcium, Phosphorus, Magnesium, Sodium, Potassium, Chloride
  • Microminerals (1-100 mg/day): Iron, Zinc, Copper, Fluoride, Manganese
  • Trace minerals (<1 mg/day): Iodine, Selenium, Chromium, Molybdenum, Cobalt - Yamada's Textbook of Gastroenterology 7e, p. 993

CALCIUM

Functions:
  • Bone and teeth structure (99% of body calcium is in bone as hydroxyapatite).
  • Muscle contraction (including cardiac muscle).
  • Neuromuscular transmission.
  • Blood clotting (coagulation cascade cofactor).
  • Intracellular signaling (second messenger).
  • Enzyme activation.
Daily requirement: 1000 mg (adults 19-50), 1200 mg (women >50, all adults >70). Sources: Dairy products, fortified juices, leafy green vegetables, beans.
Deficiency:
  • Hypocalcemia: tetany, muscle cramps, Chvostek sign, Trousseau sign, seizures, prolonged QT interval.
  • Long-term: osteoporosis, osteomalacia.
Excess: Hypercalcemia: constipation, kidney stones, bone pain, confusion ("stones, bones, groans, thrones, and psychic moans").

PHOSPHORUS

Functions:
  • Bone/teeth mineralization (hydroxyapatite).
  • Component of ATP (energy currency), nucleic acids (DNA/RNA), phospholipids (cell membranes).
  • Acid-base buffer (phosphate buffer system).
  • Enzyme regulation via phosphorylation.
Daily requirement: ~700 mg. Sources: Widespread - meat, dairy, nuts, legumes, grains.
Deficiency (hypophosphatemia): Muscle weakness, hemolytic anemia, bone pain, impaired immune function. Seen in refeeding syndrome and vitamin D deficiency.

MAGNESIUM

Functions:
  • Cofactor for >300 enzyme reactions, including all ATP-generating reactions (ATP exists as Mg-ATP complex).
  • DNA and protein synthesis.
  • Muscle relaxation (calcium antagonist).
  • Nerve conduction and neuromuscular junction.
  • Regulates cardiac rhythm.
Daily requirement: 400-420 mg (men), 310-320 mg (women). Sources: Green vegetables, whole grains, nuts, legumes, dairy.
Deficiency:
  • Muscle cramps, tremors, tetany
  • Cardiac arrhythmias (including torsades de pointes)
  • Hypokalemia and hypocalcemia (refractory to replacement until Mg is corrected)
  • Neuropsychiatric symptoms: anxiety, depression, confusion
  • Common in alcoholism, chronic diarrhea, diuretic use, poorly controlled diabetes.

IRON

Functions:
  • Oxygen transport - component of hemoglobin (carries O2) and myoglobin (stores O2 in muscle).
  • Electron transport - iron-sulfur proteins in mitochondrial respiratory chain.
  • Enzyme cofactor - cytochromes, catalase, peroxidase, myeloperoxidase.
  • DNA synthesis (ribonucleotide reductase).
Daily requirement: 8 mg (men), 18 mg (premenopausal women). Sources: Meat, fish, poultry (heme iron - better absorbed), fortified cereals, legumes, spinach (non-heme iron).
Deficiency:
  • Most common nutritional deficiency worldwide.
  • Microcytic hypochromic anemia, fatigue, pallor.
  • Pica (craving for ice, dirt, clay).
  • Koilonychia (spoon-shaped nails), glossitis, angular stomatitis.
  • Impaired cognitive development in children.
  • Restless leg syndrome.
Toxicity: Hemochromatosis - liver cirrhosis, diabetes, cardiomyopathy, bronze skin.

ZINC

Functions:
  • Cofactor for >300 enzymes (DNA polymerase, RNA polymerase, alkaline phosphatase, carbonic anhydrase).
  • Immune function - critical for T-cell development and lymphocyte function.
  • Wound healing and tissue repair.
  • Taste and smell (gustin protein requires zinc).
  • Growth and sexual maturation.
  • Antioxidant (component of Cu/Zn superoxide dismutase).
Daily requirement: 11 mg (men), 8 mg (women). Sources: Oysters (richest source), red meat, poultry, beans, nuts, fortified cereals.
Deficiency:
  • Growth retardation, delayed puberty.
  • Acrodermatitis enteropathica (periorificial and acral dermatitis).
  • Alopecia.
  • Impaired wound healing.
  • Ageusia (loss of taste), anosmia.
  • Diarrhea.
  • Immune dysfunction, increased infection susceptibility.
  • Seen in malabsorption syndromes, Crohn's disease, alcoholism.

COPPER

Functions:
  • Cofactor for cytochrome c oxidase (mitochondrial respiration), superoxide dismutase (antioxidant defense), ceruloplasmin (iron transport), dopamine beta-hydroxylase, and lysyl oxidase (collagen cross-linking).
Daily requirement: ~900 μg. Sources: Meat, grain, nuts, shellfish.
Deficiency:
  • Microcytic anemia (impaired ceruloplasmin-mediated iron metabolism)
  • Neutropenia
  • Neurologic manifestations: myelopathy, peripheral neuropathy (can mimic B12 deficiency)
  • Osteoporosis
  • Defective collagen cross-linking (connective tissue abnormalities)
  • Seen after bariatric surgery, excess zinc supplementation (zinc competes with copper absorption).
Toxicity: Wilson's disease - hepatic cirrhosis, neuropsychiatric symptoms, Kayser-Fleischer rings in eyes.

IODINE

Functions:
  • Sole function: synthesis of thyroid hormones (T3 and T4), which regulate basal metabolic rate, growth, development, and thermogenesis.
Daily requirement: 150 μg (adults), 220 μg (pregnant), 290 μg (lactating). Sources: Seafood, iodized salt, dairy. Soil and water content varies widely by region.
Deficiency:
  • Goiter (enlarged thyroid gland as compensatory response).
  • Hypothyroidism - fatigue, cold intolerance, weight gain, constipation, bradycardia.
  • Cretinism (in infants born to iodine-deficient mothers) - severe irreversible intellectual disability, deaf-mutism, spastic diplegia. The leading preventable cause of intellectual disability worldwide.
Toxicity: Jod-Basedow phenomenon (iodine-induced hyperthyroidism in previously iodine-deficient patients).

SELENIUM

Functions:
  • Component of selenoproteins, including glutathione peroxidase (major antioxidant enzyme protecting against lipid peroxidation) and iodothyronine deiodinase (converts T4 to active T3).
  • Supports immune function.
  • May have anti-carcinogenic properties.
Daily requirement: 55 μg. Sources: Brazil nuts (very rich), seafood, meat, cereals (depends on soil selenium content).
Deficiency:
  • Keshan disease - endemic cardiomyopathy (first described in selenium-deficient regions of China).
  • Kashin-Beck disease - endemic osteoarthropathy.
  • Hypothyroidism (impaired T4-to-T3 conversion).
  • Immune dysfunction.
Toxicity (selenosis): Garlic breath, hair and nail loss, nausea, peripheral neuropathy.

CHROMIUM

Functions:
  • Potentiates the action of insulin by facilitating glucose uptake into cells.
  • Cofactor for glucose tolerance factor (GTF).
  • Involved in lipid and protein metabolism.
Daily requirement: 25-35 μg. Sources: Whole grains, broccoli, meat, brewer's yeast.
Deficiency: Impaired glucose tolerance, peripheral neuropathy (rare; mainly described in long-term parenteral nutrition without chromium supplementation).

MANGANESE

Functions:
  • Cofactor for arginase (urea cycle), pyruvate carboxylase, manganese superoxide dismutase (mitochondrial antioxidant), and glycosyltransferases (proteoglycan synthesis).
  • Bone development and wound healing.
Sources: Whole grains, nuts, legumes, leafy vegetables, tea.
Deficiency: Extremely rare. Impaired growth, skeletal abnormalities, altered carbohydrate and lipid metabolism.

FLUORIDE

Functions:
  • Incorporates into hydroxyapatite to form fluorapatite, which is harder and more acid-resistant - the basis of tooth decay prevention.
  • Strengthens bones.
Sources: Fluoridated water, tea, seafood, fluoride toothpaste.
Deficiency: Dental caries (tooth decay).
Toxicity (fluorosis): Dental fluorosis (mottled teeth), skeletal fluorosis (dense but brittle bones) with excessive intake.

MOLYBDENUM

Functions:
  • Cofactor for xanthine oxidase (purine catabolism to uric acid), sulfite oxidase (sulfur amino acid metabolism), and aldehyde oxidase.
Daily requirement: 45 μg. Sources: Legumes, grain, nuts.
Deficiency: Essentially unknown in free-living humans; reported only in patients on total parenteral nutrition (TPN) without molybdenum - causes neurologic dysfunction and tachycardia.

QUICK REFERENCE SUMMARY TABLE

Vitamin/MineralKey FunctionDeficiency Disease/Sign
Vitamin AVision, epithelial differentiationNight blindness, xerophthalmia
Vitamin DCalcium homeostasis, bone mineralizationRickets (children), osteomalacia (adults)
Vitamin EAntioxidant, membrane protectionHemolytic anemia, ataxia
Vitamin KClotting factor activation, boneBleeding, hemorrhagic disease of newborn
Vitamin CCollagen synthesis, antioxidantScurvy
Thiamine (B1)Energy metabolism (pyruvate decarboxylation)Beriberi, Wernicke-Korsakoff
Riboflavin (B2)FAD/FMN (redox reactions)Ariboflavinosis, glossitis
Niacin (B3)NAD+/NADP+ (400+ reactions)Pellagra (4 Ds)
B6 (Pyridoxine)Amino acid metabolism, neurotransmittersSideroblastic anemia, neuropathy, seizures
Folate (B9)DNA synthesis, cell divisionMegaloblastic anemia, neural tube defects
B12 (Cobalamin)DNA synthesis, myelin maintenanceMegaloblastic anemia + subacute combined degeneration
Biotin (B7)Carboxylase reactionsAlopecia, dermatitis (rare)
Pantothenic acid (B5)CoA component, energy metabolismBurning feet syndrome (very rare)
CalciumBone, muscle contraction, signalingTetany, osteoporosis
PhosphorusATP, nucleic acids, boneMuscle weakness, hemolytic anemia
Magnesium300+ enzymes, muscle relaxationArrhythmia, tetany, hypokalemia
IronHemoglobin, electron transportMicrocytic anemia
Zinc300+ enzymes, immunity, wound healingGrowth failure, dermatitis, anosmia
CopperCytochrome oxidase, ceruloplasminAnemia, neutropenia, myelopathy
IodineThyroid hormone synthesisGoiter, hypothyroidism, cretinism
SeleniumGlutathione peroxidase (antioxidant)Keshan disease (cardiomyopathy)
ChromiumInsulin potentiationImpaired glucose tolerance
FluorideDental/bone strengthDental caries
ManganeseArginase, SOD, bone developmentRare - skeletal abnormalities
MolybdenumXanthine oxidase, sulfite oxidaseExtremely rare
Key clinical pearls:
  • Fat-soluble vitamin deficiency (A, D, E, K) occurs together in fat malabsorption syndromes (celiac disease, Crohn's, chronic pancreatitis, cholestasis).
  • B12 deficiency causing neurological symptoms (unlike folate) is a critical distinguishing feature.
  • Giving folate to a B12-deficient patient corrects the anemia but allows the neurological damage to progress - always rule out B12 deficiency first.
  • Zinc excess can cause copper deficiency by competitive inhibition of absorption.
  • Patients after bariatric surgery are at high risk for B vitamins (especially B1, B12), iron, zinc, calcium, and vitamin D deficiencies. - Fischer's Mastery of Surgery 8e
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