Fat-Soluble Vitamins

Fat-Soluble Vitamins

1. Definition, classification & the fat-soluble vs water-soluble divide

• Vitamins are non-energy-yielding organic compounds, essential for normal human metabolism, that must be supplied in small quantities in the diet; the definition excludes the inorganic trace minerals and the essential amino acids/fatty acids (needed in much larger amounts) (KDT 8e Ch.69, p.968).
• The different chemical forms and precursors of a given vitamin are its vitamers (analogy — isomers); e.g. retinol (A₁), dehydroretinol (A₂) and β-carotene (provitamin) are all vitamers of vitamin A (KDT 8e Ch.69, p.968).
• The pharmacological importance of vitamins is primarily prophylaxis and treatment of deficiency states; some have additional empirical uses at pharmacological (supra-physiological) doses (KDT 8e Ch.69, p.968).
• Deficiency arises from: inadequate intake, malabsorption, increased tissue needs, increased excretion, certain genetic abnormalities, and drug–vitamin interactions (KDT 8e Ch.69, p.968).
• Vitamins as a class are over-promoted, over-prescribed and over-used; myths ("vitamins energise the body", "any illness accompanies a deficiency", "normal-diet intake is precariously marginal", "vitamins are harmless") are rampant — the last myth is specifically dangerous for the fat-soluble group (KDT 8e Ch.69, p.968).
• Traditional two-group classification (KDT 8e Ch.69, p.968):
  • (a) Fat-soluble — A, D, E, K. These (except vitamin K) are stored in the body for prolonged periods and are therefore liable to cause cumulative toxicity after regular ingestion of large amounts. Some interact with specific cellular (nuclear) receptors analogous to hormones (A and D act through nuclear receptors of the steroid/thyroid superfamily).
  • (b) Water-soluble — B complex, C. Meagrely stored; excess is excreted with little chance of toxicity; they act as cofactors for enzymes of intermediary metabolism. (Out of scope for this topic — cross-reference only.)
• The central pharmacological contrast (why fat-soluble vitamins carry a distinct toxicity risk): because A, D and E are lipophilic and stored in liver and adipose tissue, regular excess accumulates and produces cumulative hypervitaminosis (toxicity) — unlike the water-soluble vitamins whose surplus is renally cleared. Vitamin K is the exception among the fat-solubles — it is stored only to a limited extent and turns over faster (hence deficiency can appear relatively quickly when intake/synthesis stops) (KDT 8e Ch.69, p.968; daily-allowance table p.971).
• Vitamin D — pointer only. Vitamin D (calciferol D₂ / cholecalciferol D₃ / calcitriol) is a fat-soluble vitamin but its full pharmacology belongs to calcium homeostasis / bone mineral metabolism (KDT houses it in Ch.24) and it has its own dedicated topic on this site — treated here only as a member of the fat-soluble class for the toxicity/storage contrast (KDT 8e Ch.69, p.977 cross-ref "Vitamin D (Ch. 24)").

— Absorption & storage common to the fat-soluble group —

• All four fat-soluble vitamins share a bile-salt / micelle-dependent absorption pathway: dietary esters are hydrolysed in the gut, the free vitamin is incorporated into mixed micelles (requiring bile), absorbed by enterocytes, packaged into chylomicrons, and delivered via intestinal lacteals → lymph → systemic circulation (rather than the portal vein) (KDT 8e Ch.69, pp.968–970 — stated explicitly for A "aided by bile, it passes into lacteals" and E "absorbed…through lymph with the help of bile").
• Malabsorption states that impair fat-soluble vitamin uptake (a high-yield PG point): steatorrhoea, bile deficiency / cholestasis / biliary obstruction, pancreatic insufficiency, cystic fibrosis, extensive small-bowel disease, and protein-poor diets — all reduce absorption of A (and by the same mechanism D, E, K). Chronic use of liquid paraffin (mineral oil) and long-term oral neomycin (induces steatorrhoea) similarly cause fat-soluble vitamin deficiency (KDT 8e Ch.69, pp.969–970).
• Storage: vitamin A as retinyl esters and vitamin E are stored in the liver (A also in hepatic stellate cells) and adipose tissue and released slowly; deficiency symptoms therefore appear only after long-term deprivation (KDT 8e Ch.69, pp.969–970).