Vitamins. Their Role in the Human Body. G.F.M. Ball Consultant, London, UK. Blackwell Science

Transcription

1 Vitamins Their Role in the Human Body G.F.M. Ball Consultant, London, UK Blackwell Science

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3 Vitamins: Their Role in the Human Body

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5 Vitamins Their Role in the Human Body G.F.M. Ball Consultant, London, UK Blackwell Science

6 2004 by Blackwell Publishing Ltd, a Blackwell Publishing company Editorial offices: Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Tel: +44 (0) Blackwell Publishing Professional, 2121 State Avenue, Ames, Iowa , USA Tel: Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia Tel: +61 (0) The right of the Author to be identified as the Author of this Work has been asserted in accordance with the Copyright, Designs and Patents Act All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. First published 2004 Library of Congress Cataloging-in-Publication Data is available ISBN A catalogue record for this title is available from the British Library Set in 10/12 pt Minion by Sparks, Oxford, UK Printed and bound in India by Gopsons Paper Ltd, Noida The publisher s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. For further information on Blackwell Publishing, visit our website:

7 To the memory of Mariah Margaret Ball

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9 Contents Foreword Preface xiii xv 1 Historical Events Leading to the Establishment of Vitamins Introduction Early studies of nutritionally related diseases Experiments on formulated diets Naming of the vitamins 7 Further reading 7 References 7 2 Nutritional Aspects of Vitamins Definition and classification of vitamins Nutritional vitamin deficiency Stability and bioavailability of vitamins Vitamin requirements 11 Further reading 11 References 11 3 Background Physiology and Functional Anatomy Movement of solutes across cell membranes and epithelia The blood brain, blood cerebrospinal fluid and placental barriers Functional anatomy of the small and large intestine, liver and kidney Digestion and absorption Glucose transport Digestion, absorption and transport of dietary fat Neural and endocrine communication systems Structure of bone and its growth and development Cell proliferation 62 Further reading 64 References 64 4 Background Biochemistry Major degradation pathways in which B-group vitamins are involved as coenzymes 68

10 viii Contents 4.2 Amino acid utilization Defences against free radicals and other reactive species Haemostasis Atherosclerosis 80 Further reading 90 References 90 5 Background Immunology General features of the immune system Innate immunity Inflammation Acquired immunity Cytokines Hypersensitivity Immune suppression Neuroendocrine modulation of immune responses 108 Further reading 108 References The Genetic Control of Protein Synthesis and its Regulation by Nuclear Hormone Receptors Functional structure of DNA Role of RNA in protein synthesis Gene expression Mutation and polymorphism Basal transcription Regulated transcription Jun, Fos and the AP-1 complex Nuclear hormone receptors as regulators of protein synthesis 126 Further reading 131 References Vitamin A: Retinoids and Carotenoids Historical overview Chemistry and biological functions Dietary sources Absorption, transport and metabolism Nutritional factors that influence vitamin A status The role of vitamin A in vision Retinoids as regulators of gene expression Effects of vitamin A on the immune system Role of vitamin A in bone metabolism and embryonic development Vitamin A and cancer Vitamin A deficiency and toxicity 178 Further reading 180 References 180

11 Contents ix 8 Vitamin D Historical overview Chemistry and biological functions Dietary sources Cutaneous synthesis, intestinal absorption, transport and metabolism Molecular action of the vitamin D hormones Calcium and phosphate homeostasis Immunoregulatory properties Effects of vitamin D on insulin secretion Vitamin D-related diseases Therapeutic applications of vitamin D analogues Toxicity Dietary requirement 224 Further reading 224 References Vitamin E Historical overview Chemistry, biopotency and units of activity Dietary sources Absorption, transport and delivery to tissues Antioxidant role Effect upon the ageing immune responses Vitamin E and atherosclerosis Vitamin E deficiency Dietary intake 251 Further reading 252 References Vitamin K Historical overview Chemistry Dietary sources Absorption, transport and metabolism Biochemical and physiological functions Vitamin K deficiency 268 Further reading 269 References Thiamin (Vitamin B 1 ) Historical overview Chemistry and biological activity Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Neurophysiological functions Vitamin B 1 deficiency 282

12 x Contents 11.8 Nutritional aspects 286 Further reading 287 References Flavins: Riboflavin, FMN and FAD (Vitamin B 2 ) Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Vitamin B 2 deficiency Nutritional aspects 298 Further reading 299 References Niacin: Nicotinic Acid and Nicotinamide Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Niacin deficiency Nutritional aspects 308 Further reading 309 References Vitamin B Historical overview Chemistry and biological activity Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Regulation of steroid hormone action Immune function Vitamin B 6 deficiency Nutritional aspects 322 Further reading 323 References Pantothenic Acid and Coenzyme A Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions of coenzyme A and acyl carrier protein in cellular metabolism Physiological roles of coenzyme A in the modification of proteins 332

13 Contents xi 15.7 Deficiency in animals and humans Dietary intake 334 Further reading 335 References Biotin Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical and physiological functions Biotin deficiency 343 Further reading 345 References Folate Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Homocysteine-related occlusive arterial and thrombotic diseases Folate and neural tube defects Folate deficiency Dietary intake 376 Further reading 376 References Vitamin B Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Biochemical functions Vitamin B 12 deficiency Dietary intake 390 Further reading 391 References Vitamin C Historical overview Chemistry Dietary sources and bioavailability Absorption, transport and metabolism Effect of ascorbic acid upon absorption of inorganic iron Inhibition of N-nitroso compound formation Biochemical and neurochemical functions 403

14 xii Contents 19.8 Role of ascorbic acid in mesenchymal differentiation Antioxidant role Immune function Vitamin C and cardiovascular disease Vitamin C deficiency Dietary intake 415 Further reading 415 References 415 Abbreviations 421 Glossary 423 Index 429

15 Foreword The thirteen vitamins that are essential for an adequate human diet are staggeringly diverse in their structures, chemical properties and functions, but they have, by and large, all arrived at a similar juncture in their evolving recognition and understanding. Fifty to a hundred years ago, the main research emphasis was on isolation, structural determination, basic biochemical properties and functional significance. As George Ball s new book demonstrates, the quest for their functional significance is still continuing and is by no means yet complete. However, the recent focus on their public health significance has shifted from a relatively straightforward concern with the prevention and cure of overt deficiency diseases towards more subtle functional properties, often linked to those medical conditions that are not obviously vitamin-dependent. An example is folate, a generic group of compounds which includes folic acid. When discovered, its medical significance was in the prevention of megaloblastic anaemia in pregnant women in developing countries such as India. Today, the focus has shifted towards the avoidance of neural tube defects (spina bifida, anencephaly) in western countries and the reduction of hyperhomocysteinaemia, which is considered to be a precursor, predictor, and likely causative agent for vascular diseases, including some dementias. There are recent indications that folate may influence cancer risk, especially for bowel cancers. Paradoxically, whereas anti-folate drugs are frequently used to treat existing cancer, poor folate status may be a risk factor for development of new cancers, perhaps by compromising DNA repair mechanisms. None of these implications of folate status were recognized before the final decades of the twentieth century, and they are still being researched and refined. Another recently emergent research topic has involved the so-called antioxidant vitamins, prin- cipally vitamins C and E, perhaps better described as redox modulators, because they can act as prooxidants as well as antioxidants. Risk of developing degenerative diseases such as vascular disease, cancers and eye diseases (cataract, macular degeneration) has been linked to these protective nutrients via animal and tissue culture model studies and epidemiological associations. The removal of oxygen-derived reactive free radicals seems generally beneficial and desirable, and is performed efficiently by these micronutrients. Just how important this is for human health remains controversial, as is the question, how far we now need to go beyond deficiency and toward enhanced and optimal protection against noxious agents in the environment and those derived from our own metabolic processes. The fat-soluble vitamins have likewise proved equally elusive, with respect to the breadth of their functional implications. Thus, until a couple of decades ago, vitamin A was seen as the anti-xerophthalmia, anti-keratomalacia vitamin, preventing blindness in children in poor, developing countries. Then its role in preventing severe morbidity and mortality from infectious diseases was recognized, and this soon assumed dominance. Now, new roles for vitamin A in gap-junction cell cell communication and on cellsignalling are recognized, revealing a potential role for retinoids in the treatment of cancer. Derivatives of vitamin D, the sunshine vitamin which prevents rickets and osteomalacia, also have therapeutic potential for cancer. Vitamin K, which is used clinically to prevent haemorrhagic disease in breast-fed babies, now assumes important new significance for osteoporosis and arterial calcification. All these newly discovered roles for individual vitamins have serious implications for recommended dietary amounts and for public health food policies. In the UK, government recommendations for reference