The eight B vitamins function as coenzymes central to energy production, neurotransmitter synthesis, and one-carbon metabolism. Thiamine (B1), as thiamine pyrophosphate, is essential for pyruvate dehydrogenase linking glycolysis to the TCA cycle, and for branched-chain alpha-keto acid dehydrogenase in BCAA catabolism, which is why thiamine deficiency (beriberi and Wernicke-Korsakoff syndrome) is particularly devastating in alcoholics who consume few calories but require thiamine for alcohol metabolism. Riboflavin (B2), through FAD and FMN, serves as electron carrier in the electron transport chain and is required by the MTHFR enzyme, with 400 mg daily showing efficacy comparable to prescription drugs for migraine prevention. Niacin (B3) exists as nicotinic acid (which lowers LDL and raises HDL but causes flushing), nicotinamide (anti-inflammatory for skin), and NAD+ precursors (NMN and NR), which are at the forefront of longevity research because NAD+ declines roughly fifty percent between ages 40 and 60.
Vitamin B6 (pyridoxal 5'-phosphate, PLP) is the master cofactor for amino acid metabolism, required for transamination reactions, decarboxylation of aromatic amino acids into neurotransmitters (serotonin from tryptophan, dopamine from tyrosine, GABA from glutamate, and histamine from histidine), and the transsulfuration pathway that converts homocysteine to cysteine. Folate (B9) is critical for DNA synthesis (particularly thymidylate formation), neural tube closure during embryonic development (days 21 to 28), and remethylation of homocysteine to methionine. The active form, 5-methyltetrahydrofolate (methylfolate), is increasingly preferred over synthetic folic acid because it bypasses the MTHFR enzyme, which carries loss-of-function polymorphisms in 10 to 15% of the population. Vitamin B12 (cobalamin) exists in methylated, adenosylated, and hydroxylated forms, with methylcobalamin required for methionine synthase activity and adenosylcobalamin for methylmalonyl-CoA mutase in fatty acid metabolism.
Vitamin D occupies a unique position as a secosteroid hormone precursor rather than a classical vitamin. The body synthesizes vitamin D3 (cholecalciferol) in skin exposed to UVB radiation, which is then hydroxylated in the liver to 25(OH)D (the storage form measured in blood) and again in the kidney to 1,25(OH)2D (calcitriol, the active hormone). Vitamin D's classical role is calcium and phosphorus homeostasis for bone mineralization, but vitamin D receptors are present in virtually every tissue, with at least 1000 genes containing vitamin D response elements. Vitamin D modulates both innate immunity (upregulating the antimicrobial peptide cathelicidin) and adaptive immunity (shifting from pro-inflammatory Th1/Th17 toward regulatory Th2/Treg responses), with deficiency associated with increased respiratory infections, autoimmune disease, and certain cancers.
The fat-soluble vitamins A, E, and K work in balance with each other and with vitamin D. Vitamin A (retinol from animal sources or provitamin A carotenoids from plants) is essential for rhodopsin synthesis in rod cells (deficiency causes night blindness), epithelial cell differentiation, immune function, and embryonic development, but excessive preformed vitamin A is teratogenic and can cause hypervitaminosis A. Vitamin E exists in eight forms (four tocopherols and four tocotrienols), with alpha-tocopherol being the most biologically active as the primary lipid-soluble antioxidant protecting cell membranes from lipid peroxidation. Vitamin K activates vitamin K-dependent proteins through gamma-glutamyl carboxylation, including clotting factors (II, VII, IX, X), osteocalcin for bone mineralization, and matrix Gla protein that prevents vascular calcification. Vitamin K2 (particularly the MK-7 form from fermented foods) has gained attention for directing calcium into bones rather than arteries, working synergistically with vitamin D, and the combination of vitamins D and K2 represents an increasingly recognized foundation for skeletal and cardiovascular health. Vitamin C (ascorbic acid) operates as the body's primary aqueous-phase antioxidant, is essential cofactor for collagen synthesis (prolyl and lysyl hydroxylases), enhances non-heme iron absorption by two to six-fold, and supports immune cell function, though its effects on common cold prevention are more modest than popularly believed.