Antioxidants – vitamin C, vitamin E, carotenoids (NOT vitamin A), many minerals

• All detoxify dangerous free radicals
• free radicals include superoxide (O₂· ), hydroperoxyl (HO₂· ), hydroxyl (HO· ), peroxyl (ROO· ), singlet oxygen (O· )
• natural product of metabolism – e.g. xanthine oxidase – purines Þ xanthine + O₂ + H₂ Þ uric acid + H₂O₂ Þ radicals
• also occurs as response to light or heat
• also medications, anesthetics, inflammatory response, environmental pollutants, cigarette smoke, car exhaust, UV light, industrial solvents, pesticides, PAH (aromatic hydrocarbons) in food processing
• minerals are components of antioxidant enzymes:
• (1) superoxide dysmutase– Cu and Zn (cysosolic) or Mg (mitochondrial)
• (2) catalase – heme Fe
• (3) xanthene oxidase – Fe and Mg
• (4) glutathione peroxidase – selenium (see below)

• many forms, 4 tocopherols and 4 tocotrienols (unsaturated side chain)
• Different forms (a , b , g , etc.) determined by positions of methyl groups
• different forms have different metabolic activities - a tocopherol is most active (2x as active as b , 10x as active as g )
• supplements often have esters of a -tocopherol (succinate or acetate), which are easily hydrolyzed in the gut
• Source of Vitamin E: found often in plants (acts as an antioxidant for them too) – especially nuts/whole grains
• plants with high polyunsaturated fatty acids (PUFA) have more vitamin E, since PUFAs produce radicals
• this is NOT true of fish liver oils – high PUFA, low vitamin E
• Function of Vitamin E: it stops lipid peroxide chain reaction – radical + lipid-H Þ H₂O + lipid-O-O· , etc. Þ rancidity
• vitamin E associated with the lipid donates its own hydrogen to satisfy the free electron
• this produces a tocopheroxy radical, which hands off the odd electron to vitamin C (see "vitamin C," below)
• Deficiency: most significant effects are hematological (anemia – short-lived RBC’s that lyse easily when exposed to H₂O₂)
• neurological symptoms – weakness, ataxia, poor coordination, hyporeflexia; cataracts
• reproductive symptoms – degeneration of semeniferous epithelium, fetal death and resorption in utero
• skeletal muscle degeneration (resemble muscular dystrophy) and cardiac muscle degeneration in severe cases
• observed mostly in persons with failure to absorb fat (cystic fibrosis, short gut, cholestatic hepatobiliary disease)
• Excess: relatively nontoxic compared with vitamins A and D – interferes with vitamin K function at very high levels
• Disease Prevention: vitamin E reduces risk of cardiovascular disease, perhaps by decreasing LDL oxidation

• refers to many compounds functionally equivalent to ascorbic acid (most common); ascorbic acid is the most common; reversibly oxidized to dehydroascorbic acid (no loss of function)
• Many functions:
• (1) accelerates hydroxylation reactions – hydroxyproline (collagen), lys Þ carnitine, dopamineÞ norepi, tyr catabolism
• (2) powerful reducing agent – reduces iron for absorption from gut; also aminates peptide hormones (oxytocin, CCK)
• (3) antioxidant – takes free electron from vitamin E after lipid
• Source of Vitamin C: fruits/vegetables (not just citrus – cabbage, peppers, potato)
• vitamin C is heat labile and water soluble – boiling reduces its concentration dramatically, steaming less so
• Deficiency: scurvy – after 20-40 days without vitamin C – caused by deficiency in hydroxyproline in collagen
• symptoms: weakness, fatigue, petechiae (tiny hemorrhages), ecchymoses (easily bruised), perifollicular hemorrhages, hyperkeratosis of hair follicles, swollen bleeding gums
• does not take much vitamin C to correct – just a few days of normal diet
• smoking causes reduced plasma concentration (possibly radicals accelerate turnover) – RDA is higher for smokers
• Excess: kidney stones, rebound scurvy when large doses stopped, venous stasis, increased hemolysis, diarrhea
• Disease Prevention: vitamin C is thought to improve immune system function, but no clear in vivo data

• important component of enzyme glutathione peroxidase
• exists in several forms: reduced (selenide, selenite, selenate), amino acid (selenocysteine, selenomethionine)
• degrades H₂O₂ and RO-OH before they become radicals (backup system to vitamin E) – GS-H + H₂O₂ Þ 2H₂O + GS-SG
• Deficiency: usually caused by deficient selenium in water and soil of that geographic area – does not affect plant health
• South Island of New Zealand – sheep die due to skeletal muscular dystrophy-like symptoms, population had low Se
• inland China – Keshan disease of young children (no cross-distribution of food) – fatal cardiomyopathy
• U.S. widely variable – wheat samples vary by 100 fold from different regions – low Se in Ohio, so add to turkey feed
• also due to processing of grain – Se only in germ part of whole grain, so removed during processing
• Most common cases in U.S. is extended total parenteral nutrition in which not all minerals included (= malpractice)
• leads to muscle wasting (elevated creatine kinase/transaminases)
• Excess: garlic breath odor (Se compounds), hair loss, nail changes (white streaks/tenderness/swelling), nausea, fatigue, irritability
• Disease Prevention: marked reduction in risk of cancer in animals
• humans: no reduced squamous/basal cell carcinoma risk, but reduction in colorectal, lung, and prostate cancers, and total cancer mortality