caa a22 4500 475773195 CHVBK 20180406123623.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s001250051536 doi (NATIONALLICENCE)springer-10.1007/s001250051536 Safety of high-dose nicotinamide: a review [Elektronische Daten] [M. Knip, I. F. Douek, W. P. T. Moore, H. A. Gillmor, A. E. M. McLean, P. J. Bingley, E. A. M. Gale] Nicotinamide, the amide derivative of nicotinic acid, has over the past forty years been given at high doses for a variety of therapeutic applications. It is currently in trial as a potential means of preventing the onset of Type I (insulin-dependent) diabetes mellitus in high-risk, first-degree relatives. Nicotinamide is for regulatory purposes classed as a food additive rather than a drug and has not therefore required the formal safety evaluation normally expected of a new therapy. Because the safety of treatment with megadoses of vitamins cannot be assumed, a full literature review has been undertaken. The therapeutic index of nicotinamide is wide but at very high doses reversible hepatotoxicity has been reported in animals and humans. Minor abnormalities of liver enzymes can infrequently occur at the doses used for diabetes prevention. There is no evidence of teratogenicity from animal studies and nicotinamide is not in itself oncogenic; at very high doses it does however potentiate islet tumour formation in rats treated with streptozotocin or alloxan. There is no evidence of oncogenicity in man. Growth inhibition can occur in rats but growth in children is unaffected. Studies of its effects on glucose kinetics and insulin sensitivity are inconsistent but minor degrees of insulin resistance have been reported. The drug is well tolerated, especially in recent studies which have used relatively pure preparations of the vitamin. Experience to date therefore suggests that the ratio of risk to benefit of long-term nicotinamide treatment would be highly favourable, should the drug prove efficacious in diabetes prevention. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged. [Diabetologia (2000) 43: 1337-1345] Springer-Verlag Berlin Heidelberg, 2000 Keywords Type I diabetes, nicotinamide, prevention nationallicence Knip M. Department of Paediatrics, Medical School, University of Tampere, Finland, FI aut Douek I. F. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut Moore W. P. T. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut Gillmor H. A. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut McLean A. E. M. Department of Clinical Pharmacology, University College London Medical School, UK, GB aut Bingley P. J. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut Gale E. A. M. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut https://doi.org/10.1007/s001250051536 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051536 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knip M. Department of Paediatrics, Medical School, University of Tampere, Finland, FI aut NATIONALLICENCE 700 1- Douek I. F. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut NATIONALLICENCE 700 1- Moore W. P. T. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut NATIONALLICENCE 700 1- Gillmor H. A. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut NATIONALLICENCE 700 1- McLean A. E. M. Department of Clinical Pharmacology, University College London Medical School, UK, GB aut NATIONALLICENCE 700 1- Bingley P. J. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut NATIONALLICENCE 700 1- Gale E. A. M. Diabetes and Metabolism, Division of Medicine, University of Bristol, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer