Vitamin A

Since the 1970s there has been an intense interest in studying vitamin A as an active chemopreventive agent. Observational epidemiological studies have not shown consistent cancer-preventive effects. Vitamin A, often in combination with other compounds, has been studied in several randomized trials. Overall, there is little evidence that supplementation for a few years would reduce the risk of any type of cancer. This book summarizes and evaluates the existing evidence on the cancer-preventive activity of vitamin A following the meeting of a working group of international experts in Lyon, on the 13-19 May 1998, to evaluate the existing evidence on the cancer-preventive activity of retinol and retinyl esters.

Table of Contents:
1. Chemical and physical characteristics of Vitamin A; 1.1 Retinol; 1.1.1 Name; 1.1.2 Structural and molecular formulae and relative molecular mass; 1.1.3 Physical and chemical properties; 1.1.4 Technical properties; 1.2 Retinyl Acetate; 1.2.1 Name; 1.2.2 Structural and milecular formulae and relative molecular mass; 1.3 Retinyl Palmitate; 1.3.2 Structural and molecular formulae and relative molecular mass; 1.3.3 Physical and chemical properties; 1.3.4 Technical products; 1.4 Retinal; 1.4.1 Name; 1.4.2 Structure and relative molecular mass; 1.5 Retinoic acid; 1.5.1 Name; 1.5.2 Structural and molecular formula and relative molecular mass; 1.5.3 Physical and chemical properties; 2. Occurrence, Production, Use, Analysis and Human Exposure; 2.1 Occurrence; 2.2 Production; 2.3 Use and application; 2.4 Human exposure; 2.5 Analysis; 2.5.1 Functional methods; 2.5.1.1 Night-blindness; 2.5.1.2 Conjunctival impression of cytology; 2.5.2 Biochemical methods; 2.5.2.1 Relative dose response; 2.5.2.2 Modified relative dose response; 2.5.2.3 Serum retinol; 2.5.2.4 Vitamin A in food; 2.5.2.5 Milk analysis; 3. Metabolism,kinetics, tissue distribution and inter-and intra-species variation; 3.1 Human studies; 3.1.1 Introduction; 3.1.2 Absorption; 3.1.3 Transport; 3.1.3.1 Factors affecting plasma retinoid concentrations; 3.1.4 Uptake by tissues; 3.1.5 Tissue distribution; 3.1.6 Metabolism; 3.1.7 Function; 3.1.8 Excretion; 3.1.9 Kinetics; 3.2 Experimental models; 3.2.1 Overview; 3.2.1.1 Animal models; 3.2.1.2 Vitamin A metabolism and transport; 3.2.2 Intestinal uptake and metabolism of dietray vitamin A; 3.2.2.1 Provitamin A carotenoid uptake and metabolism; 3.2.2.2 Preformed vitamin A uptake and metabolism; 3.2.3 Chylomicron delivery of postprandial vitamin A; 3.2.3.1 Overview; 3.2.3.2 Hepatic clearance; 3.2.4 Hepatic storage and metabolism of vitamin A; 3.2.4.1 Hepatic processing of dietary vitamin A; 3.2.4.2 Vitamin A storage and metabolism in hepatocytes; 3.2.4.3 Transfer of vitamin A between hepatocytes and stellate cells; 3.2.4.4 Vitamin A storage and metabolism in hepatic stellate cells; 3.2.4.5 Hepatic mobilization and plasma transport of retinol:retinol-binding protein; 3.2.4.6 Hepatic retinoic acid formation and metabolism; 3.2.5 Plasma transport of vitamin A; 3.2.5.1 Retinol delivery to target tissues; 3.2.5.2 Plasma retinoic acid; 3.2.5.3 Plasma 13-cis-retinoic acid; 3.2.5.4 Plasma 9-cis-retinoic acid; 3.2.5.5 Retinoid glucuronides; 3.2.5.6 other metabolites of retinol; 3.2.5.7 Lipoprotein-bound retinyl ester; 3.2.6 Extrahepatic vitamin A storage and metabolism; 3.2.6.1 Adipose tissue; 3.2.6.2 Kidney; 3.2.6.3 Testis; 3.2.6.4 Lung; 3.2.6.5 Bone marrow; 3.2.6.6 Eye; 3.2.6.7 Other tissues and species; 3.2.7.1 Retinoic acid formation in tissues; 3.2.7.2 Synthesis of retinoic acid from carotenoids within tissues; 3.2.7.3 Metabolism of retinoic acid; 4. Preventive effects; 4.1. Humans; 4.1.1 Epidemiological studies; 4.1.1.1 Methodological issues; 4.1.1.2 Assessment of exposure; 4.1.1.3 Vitamin A and specific cancer sites; 4.1.2 Intervention trials with cancer as an endpoint; 4.1.2.1 Primary prevention trials; 4.1.2.2 Prevention of second primary cancers; 4.1.3 Preneoplastic lesions and intermediate end-points; 4.1.3.1 Oral premalignancy; 4.1.3.2 Reversal of oral premalignancy; 4.1.3.3 Larynx; 4.1.3.4 Oesophagus and stomach; 4.1.3.6 Lung; 4.1.3.7 Cervical dysplasia; 4.1.3.8 Systemic biomarkers; 4.1.3.9 Summary; 4.2 Experimental models; 4.2.1 Tumour induction; 4.2.1.1 Lung; 4.2.1.2 Mammary gland; 4.2.1.3 Urinary bladder; 4.2.1.4 Skin; 4.2.1.5 Oesophagus and forestomach; 4.2.1.6 Large intestine; 4.2.1.7 Liver; 4.2.1.8 Thyroid; 4.2.1.9 Other Sites; 4.2.2 Intermediate biomarkers; 4.2.3 In vitro models; 4.2.3.1 Modulation of cell proliferation and differentiation; 4.3 Mechanism of chemoprevention; 4.3.1 Inhibition of events associated with carcinogenesis; 4.3.1.1 Effects of premalignant lesions; 4.3.1.2 Inhibition of transformation; 4.3.1.3 Inhibition of DNA sythesis and cell proliferation; 4.3.1.4 Inhibition of ornithine decarboxylase induction; 4.3.1.5 Restoration of normal differentiation; 4.3.1.6 Restoration of gap junctional communication; 4.3.1.7 Inhibition of prostaglandin production; 4.3.1.8 Modulation of cell adhesion and migration; 4.3.2 Inhibition of antiogenesis; 4.3.3 Modulation of immune responses; 4.3.4 Missing; 4.3.5 other Mechanisms; 5. Other Beneficial effects; 5.1 Conditions related to vitamin A deficiency; 5.1.1 Night-blindness and xerophtalmia; 5.1.2 growth; 5.1.3 Cystic fibrosis; 5.1.4 psoriasis and other skin conditions; 5.1.5 Anaemia; 5.1.6 Eclampsia and abruptio placentae; 5.2 Infectious disease and mortality; 5.3 Effects on vascular or heart disease; 5.4 Other preventive actions; 5.4.1 Degenerative conditions of ageing; 5.4.2 Arthritis; 5.4.3 other protective antioxidant effects; 5.4.5 Lung function; 6. Carcinogenicity; 6.1 Human studies; 6.2 Experimental models; 7. Other Toxic effects; 7.1 Toxic and other adverse effects; 7.1.1 Human Studies; 7.1.1.1 Mucucutaneous toxicity; 7.1.1.2 Circulatory toxicity; 7.1.1.3 Internal organ toxicity; 7.1.1.4 Neurological toxicity; 7.1.2 Experimental studies; 7.1.2.1 Mucocutaneous toxicity; 7.1.2.2 Circulatory toxicity; 7.1.2.3 internal organ toxicity; 7.1.2.4 Musculo-skeletal toxicity; 7.2 Reproductive and developmental effects; 7.2.1 Human studies; 7.2.2 Experimental studies; 7.2.2.1 Effects on embryonic development; 7.2.2.2 Interspecies comparison of the metabolism and bioactivation of vitamin A following teratogenic doses; 7.2.2.3 Role of vitamin A in reprodcution, in particular spermatogenesis; 7.2.2.4 Possible metabolic basis of retinoi-induced teratogenicity; 7.3 Genetic and related effects; 7.3.1 Human studies; 7.3.2 Experimental studies; 8. Summary of Data; 8.1 Chemistry, occurrence and human exposure; 8.2 Metabolism and kinetic properties in humans and animals; 8.3 Cancer preventive effects; 8.3.1 Human studies; 8.3.2 Experimental studies; 8.4 Other beneficial effects; 8.5 Carcinogenic effects; 8.5.1 Human studies; 8.5.2 Experimental animals; 8.6 Toxic effects; 8.6.1 Human studies; 8.6.2 Experimental studies; 9. Recommendation for future research; 10. Evaluation; 10.1 Cancer-preventive activity; 10.1.1 Humans; 10.1.2 Experimental animals; 10.2 Overall evaluation; References; Appendix 1