Safety of vitamin A: Recent results

Citation
Uw. Wiegand et al., Safety of vitamin A: Recent results, INT J VIT N, 68(6), 1998, pp. 411-416
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Food Science/Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH
ISSN journal
0300-9831 → ACNP
Volume
68
Issue
6
Year of publication
1998
Pages
411 - 416
Database
ISI
SICI code
0300-9831(1998)68:6<411:SOVARR>2.0.ZU;2-B
Abstract
A still unresolved public health concern is that excessive vitamin A intake , like vitamin A deficiency, possibly causes birth defects not only in anim als but also in man. Due to the low incidence of possibly vitamin A-related malformations in man, available data cannot convincingly define the upper safe limit of periconceptional vitamin A intake. Direct human intervention studies are not feasible for ethical reasons. Therefore, a novel approach i n addressing this issue was chosen by combining teratogenicity data from a validated animal model with data on systemic exposure to vitamin A and its major metabolites in female volunteers. In a study in pregnant women endoge nous plasma concentrations of vitamin A metabolites during early pregnancy ranged from 0.26 to 7.72 ng/ml. Since they did not cause any foetal malform ations, retinoid plasma levels in this range can be considered non-teratoge nic. Results of a trial in non-pregnant women document that daily oral vita min A supplements of 4000, 10000 and 30000 IU given for 3 weeks were in the range or slightly above the range of endogenous plasma levels seen in earl y pregnancy. Even after a 3-week treatment with 30000 IU/day, peak plasma l evels of retinoic acid and isotretinoin were within or just slightly above the range of their physiological levels. In cynomolgus monkeys (average wei ght: 3-4kg), a NOAEL (no observed adverse effect level) of 7500 IU per kg b ody weight and a LOAEL (lowest observed adverse effect level) for developme ntal toxicity of 20000 IU/kg was found. Considering these results in the cy nomolgus monkey, a dose of 30000 IU/day should also be considered as non-te ratogenic in man.