Vitamins, Minerals & Cofactors

Vitamins are organic compounds required in small amounts for normal metabolic function that the body cannot synthesise in sufficient quantities — they must be obtained from the diet. The word comes from "vital amines" — a historical (if not entirely accurate) description of their importance. There are 13 essential vitamins, divided into two groups by their solubility: Fat-soluble vitamins: A, D, E, K - Absorbed with dietary fat in the small intestine - Stored in the liver and fatty tissues — the body can accumulate reserves - Deficiency develops slowly (months to years) because of reserves - Toxicity is possible from excess supplementation (especially A and D) — because they are stored rather than excreted Water-soluble vitamins: C and B vitamins (B1, B2, B3, B5, B6, B7, B9, B12) - Absorbed directly into the bloodstream - NOT stored (except B12, which has a few years' reserve in the liver) - Excess is excreted in the urine — toxicity is rare - Deficiency develops relatively quickly without regular intake Why do vitamins matter biochemically? Most vitamins serve as cofactors or coenzymes — they assist enzymes in carrying out reactions. Without them, metabolic pathways stall. Every B vitamin is a cofactor for key metabolic reactions — particularly in the Krebs cycle and energy metabolism. This is why B vitamin deficiencies affect energy production and rapidly dividing tissues (gut lining, bone marrow, nervous system) first.

The B vitamins are a family of 8 water-soluble vitamins, most of which act as coenzymes in energy metabolism. Vitamin B1 (Thiamine): Cofactor for pyruvate dehydrogenase (the enzyme converting pyruvate → Acetyl-CoA) and alpha-ketoglutarate dehydrogenase (in the Krebs cycle). Without it, glucose cannot be fully metabolised. Deficiency causes Beriberi — nervous system and heart failure. Two forms: - Wet beriberi: heart failure with oedema - Dry beriberi: peripheral neuropathy Wernicke-Korsakoff syndrome — acute thiamine deficiency in alcoholics (alcohol prevents absorption and use of thiamine). Wernicke's: acute confusion, eye movement abnormalities, unsteady gait. Korsakoff's: chronic memory disorder. Treated urgently with IV thiamine — before giving any glucose, as glucose metabolism consumes the last remaining thiamine. Vitamin B3 (Niacin): Precursor to NAD⁺ and NADP⁺ — the essential electron carriers in glycolysis, Krebs cycle, and the ETC. Without niacin, energy production across the entire cell fails. Deficiency causes Pellagra — the "4 Ds": Dermatitis, Diarrhoea, Dementia, Death. Historically common in populations subsisting on corn (maize has niacin in a bound, unabsorbable form). Vitamin B9 (Folate/Folic Acid): Essential for DNA synthesis — specifically for making thymidine (the T base in DNA). Without folate, rapidly dividing cells cannot make DNA properly. Deficiency causes megaloblastic anaemia — red blood cells are enlarged and fewer in number because they cannot divide properly (stuck in a large immature form). Neural tube defects (spina bifida, anencephaly) occur when folate is deficient in the first weeks of pregnancy — before many women know they are pregnant. This is why folate supplementation is recommended for all women planning pregnancy. Vitamin B12 (Cobalamin): Required alongside folate for DNA synthesis; also essential for myelin synthesis in nerve fibres. Sources: Exclusively animal products (meat, fish, eggs, dairy) — strict vegans are at risk. Deficiency causes: Megaloblastic anaemia (same as folate deficiency) PLUS subacute combined degeneration of the spinal cord — degeneration of the posterior and lateral columns, causing numbness, weakness, and eventually paralysis. Pernicious anaemia — autoimmune destruction of gastric parietal cells → no intrinsic factor → B12 cannot be absorbed in the ileum. Treated with intramuscular B12 injections bypassing the defective absorption.

Vitamin C (Ascorbic Acid): A powerful antioxidant that donates electrons to neutralise reactive oxygen species (free radicals) that would otherwise damage DNA, proteins, and membranes. Key biochemical role: hydroxylation of proline in collagen synthesis. Without Vitamin C, collagen triple helices cannot form properly → weak connective tissue throughout the body. Scurvy — Vitamin C deficiency. Classic in historical seafarers deprived of fruit for months. Features: bleeding gums, poor wound healing, perifollicular haemorrhages (bleeding around hair follicles), joint pain, fragile blood vessels. Rapidly fatal without treatment. Treated simply with fresh fruit or Vitamin C supplements. --- Vitamin D: Unique because it functions more like a hormone than a vitamin. It is synthesised in the skin when UV-B light converts 7-dehydrocholesterol → cholecalciferol (Vitamin D3). This undergoes hydroxylation in the liver (25-hydroxylation) then again in the kidney (1-alpha-hydroxylation) to form the active form: 1,25-dihydroxycholecalciferol (calcitriol). Main function: Promotes calcium and phosphate absorption from the gut (by inducing calcium-binding proteins in intestinal cells). Essential for bone mineralisation. Deficiency causes: - Rickets in children — soft, deformed bones (bow legs, skull deformity) - Osteomalacia in adults — soft bones, bone pain and tenderness - Osteoporosis risk in the elderly — inadequate calcium absorption accelerates bone loss Very common in northern climates (insufficient UV-B in winter), darker skin (melanin reduces UV-B penetration), and housebound elderly. Supplementation is widely recommended. --- Vitamin K: Essential cofactor for the activation of clotting factors II, VII, IX, and X (and proteins C and S). Vitamin K enables carboxylation of glutamate residues in these proteins — without this, they cannot bind calcium and therefore cannot participate in the clotting cascade. Clinical uses of Vitamin K antagonism: Warfarin blocks Vitamin K recycling → clotting factors not activated → anticoagulation. Used to prevent clots in atrial fibrillation, deep vein thrombosis, and mechanical heart valves. Vitamin A: Essential for: vision (rhodopsin synthesis in rod cells), immune function, epithelial cell differentiation, and embryonic development. Night blindness is the earliest sign of deficiency — rhodopsin cannot be regenerated without Vitamin A. Progresses to xerophthalmia (dry eyes) and corneal ulceration. A leading cause of preventable blindness worldwide, particularly in developing countries. Toxicity: Excess Vitamin A (retinol) is teratogenic (causes birth defects) — high-dose supplements are contraindicated in pregnancy.

Minerals are inorganic elements required for a wide range of biochemical functions. Unlike vitamins, they are not broken down by cooking. Key minerals include: Iron (Fe): The most common nutritional deficiency worldwide. Iron is the central atom in haem — the oxygen-carrying part of haemoglobin and myoglobin. It is also an essential component of cytochromes in the electron transport chain. Absorption: Iron is absorbed in the small intestine. Haem iron (from meat) is absorbed 3× better than non-haem iron (from plants). Vitamin C enhances non-haem iron absorption (reduces Fe³⁺ to Fe²⁺, the absorbable form); tea/coffee inhibit it (tannins bind iron). Iron-deficiency anaemia: Small, pale (microcytic, hypochromic) red blood cells. Symptoms: fatigue, breathlessness, pallor, hair loss, brittle nails, pica (craving non-food items). Iron overload (haemochromatosis): Most commonly hereditary (HFE gene mutation). Iron accumulates in liver, heart, pancreas, joints, skin ("bronze diabetes" — liver cirrhosis + diabetes + skin bronzing). Treatment: regular venesection (blood removal). Calcium (Ca²⁺): 99% stored in bone (as hydroxyapatite). In the blood, calcium is critical for: muscle contraction (including heart), nerve transmission, blood clotting, and enzyme activation. Hypocalcaemia: Muscle cramps, tetany (involuntary muscle spasms), perioral tingling, seizures. Causes: Vitamin D deficiency, hypoparathyroidism. Hypercalcaemia: "Bones, stones, groans, and psychic moans" — bone pain, kidney stones, constipation/nausea, confusion/depression. Most commonly caused by hyperparathyroidism or malignancy. Iodine: Essential component of thyroid hormones T3 and T4. Without iodine, the thyroid cannot make hormones → hypothyroidism + goitre (the thyroid enlarges as it tries to work harder). Iodine deficiency is the most common preventable cause of intellectual disability worldwide — severe deficiency during pregnancy causes cretinism. Salt iodisation programmes have dramatically reduced global prevalence. Zinc: Cofactor for >300 enzymes, including DNA and RNA polymerases and carbonic anhydrase. Essential for immune function, wound healing, taste, and smell. Deficiency causes: poor wound healing, immune deficiency, hair loss, diarrhoea, and loss of taste/smell (ageusia/anosmia).

Free radicals are molecules with an unpaired electron — making them highly reactive. They steal electrons from nearby molecules, damaging them and creating more free radicals in a chain reaction. Reactive oxygen species (ROS) — the main free radicals in biology: - Superoxide (O₂•⁻) — produced as a byproduct of the ETC - Hydrogen peroxide (H₂O₂) — less reactive, can generate more dangerous radicals - Hydroxyl radical (•OH) — the most reactive; attacks DNA, proteins, and lipids indiscriminately Sources of ROS: - Normal metabolism (ETC "leaks" electrons — 1–5% of O₂ consumed becomes superoxide) - Inflammation (white blood cells deliberately generate ROS to kill bacteria) - Environmental: UV radiation, cigarette smoke, pollutants, alcohol metabolism Damage caused by ROS (oxidative stress): - DNA damage — base modifications, strand breaks → mutations, cancer - Lipid peroxidation — ROS attack fatty acids in membranes → cell membrane disruption; oxidised LDL is particularly atherogenic (drives atherosclerosis) - Protein oxidation — enzyme inactivation, protein aggregation (linked to Alzheimer's and Parkinson's) The body's antioxidant defences: - Enzymatic: Superoxide dismutase (SOD) converts O₂•⁻ → H₂O₂; Catalase converts H₂O₂ → H₂O; Glutathione peroxidase uses glutathione to neutralise peroxides - Non-enzymatic: Vitamins C and E, beta-carotene, uric acid, bilirubin - Diet-derived: Polyphenols (in berries, green tea, dark chocolate), carotenoids (in vegetables) Oxidative stress and disease: Imbalance between ROS production and antioxidant defences — an important contributor to: - Cardiovascular disease (LDL oxidation) - Cancer (DNA mutations) - Type 2 diabetes (impaired insulin signalling) - Neurodegenerative diseases (Alzheimer's, Parkinson's) - Ageing (cumulative cellular damage) The relationship between antioxidant supplementation and disease prevention is complex — high-dose supplements have sometimes proven harmful in trials, suggesting that the natural balance of redox reactions in the body is carefully regulated and cannot simply be "boosted" with megadose supplements.