Lect15+Fat+SolVitamins

Lect15+Fat+SolVitamins - Discovery Discovery of Vitamins...

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Unformatted text preview: 3/15/2010 Discovery Discovery of Vitamins Vitamins FatFat-Soluble Vitamins Discovery of vitamins showed that polished rice caused beriberi in chickens and nonpolished rice cured the disease. showed that tiny amounts of certain factors from milk were necessary for the growth of rats on a purified diet. C. Eijkman F.G. Hopkins Casimir Funk summarized the requirement for “vital amines” in the diet the requirement for vital amines the diet (in addition to CHO, protein and fat); postulated “vital amine” theory of disease, i.e. certain foods could cure diseases; 4 specific “vital amines” (vitamines) would cure: pellagra, beriberi, scurvy, rickets. 1 3/15/2010 E.V. McCollum fat-soluble substance A vital amine A Vitamin A Sir Edward Mellanby Rickets in dogs fed an oatmeal diet and kept out of sun. Cured rickets with cod liver oil. Discovered the anti-rachitic substance. (Vitamin D) 2 3/15/2010 Digestion of fatfatsoluble vitamins Fat-soluble vitamins require bile acids for absorption The small intestine absorbs fat-soluble vitamins similarly to fat vitamins similarly to fat absorption. Fat-soluble vitamins require digestive enzymes for absorption Gut bacteria produce little vitamin K Retinoids Compounds that support the physiological functions of vitamin A vitamin A = retinol retinal (visual cycle) retinoic acid (RA) All vitamin A functions (except visual cycle) 3 3/15/2010 Vitamin A (retinoids) retinal vision (nyctalopia) retinoic acid development, growth, reproduction epithelia (skin, respiratory and digestive systems, di eye xerophthalmia ) immune system nervous system carotenoids (provitamin A) liver vitamin A ester intestine vitamin A (retinol) RA effects reproduction nervous system epithelia (skin) immune function retinoic acid (RA) storage liver 4 3/15/2010 Severe vitamin A deficiency causes xerophthalmia causes xerophthalmia normal Testis Testis and vitamin A function function early deficiency severe deficiency 5 3/15/2010 + RA RA effects on newt limb regeneration regeneration ++ +++ ++++ RA effects effects on tadpole tail regrowth regrowth RA + 6 3/15/2010 Retinoids and cystic acne before after retinoid Retinoids and psoriasis vulgaris before +RA 7 3/15/2010 Effects of atRA (Renova ) on on photoaged skin 18 months topical treatment once daily before after C.N. Ellis, et al., J. Amer. Acad. Dermatology 23, 629-637 (1990). Effects Effects of retinoic acid (RA) on human human skin protective barrier epidermis –RA or old or old +RA or young RA or young dermis 8 3/15/2010 Mechanism of RA action Gene-supressed Vitamin A (retinol) RA Gene activated change in cell function new proteins Vitamin toxicity Vitamin A toxicity Recommended Dietary Allowance (RDA) (0.3 mg to 1.3 mg: age, sex, pregnancy, lactation) Toxic Intake Single dose 100-fold > RDA in adults 20-fold > in children Chronic intake 10-fold > RDA But: 60 mg on each of 2 days 81% reduction in mortality from measles in children with low vitamin A. RA is teratogenic! 9 3/15/2010 Vitamin D (cholecalciferol) The sunshine vitamin With adequate exposure to sunlight, adeq to there is no need for dietary vitamin D. 75% deficient plasma Ca++ 9-11 mg/100 ml hypocalcemia tetany mediator muscle contraction neurotransmission neurotransmission blood clotting death soft-tissue Ca++ hypercalcemia bone structure 10 3/15/2010 Vitamin D synthesis and metabolic activation skin pre-vitamin D3 blood kidney 25-OH-D3 vitamin D3 liver (calcitriol) Mechanism of calcitriol action skin Gene-suppressed Gene-suppressed calcitriol Gene activated Vitamin D liver, kidney change change in cell function function new cell proteins vitamin D regulates genes the same as retenoic acid vitamin D activates, genes, proteins produced, changes in cell function 11 3/15/2010 Intestinal function of calcitriol (1,25-dihydroxyvitamin D3) Calcitriol, the hormone produced from Vitamin D3, is the only hormone that can induce the intestine to absorb dietary Ca++. Without vitamin D and its conversion into calcitriol, dietary Ca++ absorption by the intestine is severely impaired. calcitriol stimulates intestine. without it, can't take max advantage of calcium. helps import calcium into b ody Calcitriol (1,25-dihydroxyvitamin D3) 25 hydroxy vitamin D if vitamin D, causes parathyroid hormone to be stimulated if adequate calcium, calcium into bone if restricted in calcium, will only use portion from intestine, and other portion from b one maintaining blood calcium adequate vitamin D, Calcium excess calcium goes into bone bone: resevoir of calcium, supports structure bone remodeling: bone being turned overdecalcify, calcify will die with low amounts of calcium 12 3/15/2010 insufficient to hold body weight, and bones b end ribs push out Rickets (children) or osteomalacia (adult) Causes: lack of Ca++/vitamin D; or failure to convert vitamin D into calcitriol; or failure of calcitriol to regulate gene expression. Osteomalacia vs. Osteoporosis Osteomalacia Organic bone matrix normal, but not calcified. matrix > calcium. lack of calcification Osteoporosis Matrix/calcium ratio normal, both reduced. Thin and brittle bones. reduction in total volume mass (bones shrink) thin and brittle osteopenia 13 3/15/2010 osteoporosis normal bone blood cells made in spaces spaces also repair micro fractures, a nd use it for remodeling hip replacement kills elderly risk factors: size/mass, sex, h unched-osteoporosis excercise, bed reset (hospital bed, wheelchair, space loses bone mass), race: blacks are more suseptible than asian and white Vitamin D: non-traditional functions Reproduction Anti-bacterial Psoriasis Autoimmune diseases (type I diabetes) Cancer (breast, prostate) SAD (seasonal affective disorder) 14 3/15/2010 Vitamin D Recommended Dietary Allowance (RDA) Adequate intake: 5 to 15 g/day (200-600 units) Adequate? Probably Not! Dietary need depends on skin color, sunlight exposure (intensity, time and skin surface area) and other (pregnancy, lactation)! Vitamin D-related Myths no Myth 1: Vitamin D is highly toxic 1: is highly toxic Myth 2: The RDA is realistic Myth 3: Avoid all sunlight 15 3/15/2010 Vitamin K (Koagulation) (phylloquinone) E.L. Robert Stokstad discovered vitamin K as a graduate student in Nutritional Science at Berkeley, but was prevented from publishing by his mentor. Subsequently, Heinrich Dam re-discovered vitamin K and won the Noble prize for the discovery. Dr. Stokstad continued a distinguished career in nutrition with isolation of folic acid and determination of its structure. Mechanism of vitamin K action Targeted protein (e.g. prothrombin) Vitamin K -dependent enzyme ++ modified protein binds Ca++ (e.g. thrombin) Vitamin K-dependent enzymes activate specific target proteins by enabling them to bind calcium. 16 3/15/2010 Vitamin K Functions Essential for activating proteins required for: blood clotting blood vessel repair bone density preventing soft-tissue calcification controls calcium Warfarin A vitamin K antagonist That That retards blood coagulation phlebitis retard clotting in heart value replacements Rat Poison 17 3/15/2010 Vitamin E (RRR- -tocopherol) Vitamin E is the most potent lipid-soluble anti-oxidant known. Vitamin E protects PUFA (polyunsaturated fatty acids) from oxidative damage. Vitamin E protects membranes and LDL from oxidative damage Does supplementation with higher doses of vitamin E provide health benefits? CHAOS (Cambridge Heart Antioxidant Study) St Patients with CVD dosed with 400-800 IU/day E. 77% decrease in non-fatal myocardial infarction. No reduction in CVD mortality HOPE (Heart Outcomes Prevention Evaluation) Patients with CVD or diabetes and one other risk factor dosed with 400 IU/day vitamin E. No difference in MI, stroke and CVD death 18 3/15/2010 Vitamins for Chronic Disease Prevention in Adults  Journal of the American Medical Association Vol. 287, p. 3116 (2002). A D E K Probably adequate in most North American/European populations Inadequate levels may be more common than realized; RDA likely to be inadequate No evidence of decrease in CVD mortality No evidence for supplementation need Multivitamin/mineral supplements and prevention of chronic disease. Evid. Rep. Technol. Assess. Vol. 139, p. 1 (2006). M Multivitamin/mineral supplements conferred no benefit in preventing cardiovascular disease and may prevent advanced age-related macular degeneration only in high-risk individuals.  The literature is limited on the safety of multivitamin/mineral supplements. Vitamin E and cancer. Vitamins and Hormones, Vol. 76, p. 435 (2007) randomized, double-blinded, placebo-controlled trials do not support a beneficial effect of long-term supplementation with RRR- -tocopherol or synthetic all-rac- -tocopheryl acetate forprevention of cancer 19 ...
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