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© Egil Rørvik Røsjø, 2017
Series of dissertations submitted to the Faculty of Medicine, University of Oslo
ISBN 978-82-8333-366-4
All rights reserved. No part of this publication may be
reproduced or transmitted, in any form or by any means, without permission.
Cover: Hanne Baadsgaard Utigard.
Print production: Reprosentralen, University of Oslo.
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a 25(OH)D level 100 nmol/L. Similar results were later reported in a Swedish patient cohort ZKHUHLWZDVIRXQG WKDW2+'OHYHOVRYHUFRPSDUHGWREHORZQPRO/ZHUHDVVRFLDWHGZLWKFORVHWRUHGXFWLRQLQULVNRIGLVHDVH
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Ta ble 1 . O n g o ing do uble- bli nded RC Ts o f v it a m in D
3su pple m e n tation in M S or CI S p atie nts, ordered by initiation date
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1Red u ctio n o f r elap se r ate d u ri n g th e tr ial p er io d N C T 010 247 77 N A 03.20 10/ 01.20 13* 1000 0 IU o r 40 0 IU d ai ly f o r 6 m o nt hs 40 MS
2E ffe c t o n se ru m i m mu ne m ark ers d u rin g th e tr ia l p er io d N C T 012 854 01 S O LA R 03.20 11/ 04.20 15‡ 1400 0 IU o r placeb o d aily fo r 48 w ee k s 232 RRM S
1P rop o rt io n w it h o u t d ise a se activ it y at tr ial co n cl u si o n N C T 014 400 62 EV ID IMS 12.20 11/ 03.20 15† 2040 0 IU o r 40 0 IU ev ery ot h er day f o r 18 m o n ths 80 R R M S or C IS
1C u m u la ti v e num ber of n e w T 2 lesio n s at tr ial co n cl u sio n N C T 014 905 02 N A 03.20 12/ 12.20 14† 5000 IU or 600 IU dai ly f o r 24 m o nt hs 172 RRM S
3Pro port io n w it h rel aps e du ri ng th e tr ial p er io d N C T 017 289 22 C ISA V ID 11.20 12/ 05.20 15* 1000 0 IU , 500 0 IU or pl aceb o dai ly f o r 24 w eeks 45 C IS
2E ffe c t o n se ru m i m mu ne m ark ers d u rin g th e tr ia l p er io d N C T 017 533 75 N A 01.20 13/ 07.20 14
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4Red u ctio n in relap se rate d u ri n g th e tr ial p er io d 2012- 0 0 460 2- 97 V IT A D E M 01.20 13/ ? 4000 IU or pl acebo d ai ly fo r 12 m o n ths 100 RRM S
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1Ch a n g e in ED SS af ter 6 m o nt hs N C T 018 171 66 D -L a y -M S 07.20 13/ 07.20 19 1000 00 IU or pl ace bo ev ery o the r w ee k fo r 2 4 m o nt hs 316 C IS
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'HVSLWHWKHILQGLQJVLQWKH($(PRGHO DQGWKHUHFHQWLQWHUHVWIRU7UHJDQG7KFHOOVLQ06 WKH attention toward a possible effect of vitamin A in MS has been rather limited. However, it was hypothesized in the 1980’s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WDNHQ XS E\ WKH LQWHVWLQH UHWDLQHG DQG WUDQVSRUWHG LQ WKH ERG\ DQG KDV WKH KLJKHVW ELRORJLFDO SRWHQF\ ,Q FRQWUDVWWRYLWDPLQ$DQG'YLWDPLQ(KDVQRQHHGIRUIXUWKHUPRGLILFDWLRQEHIRUHH[KLELWLQJLWVELRORJLFDOHIIHFW8SRQ dietary uptake, ĮWRFRSKHURO LV DVVHPEOHG WRJHWKHU ZLWK WULJO\FHULGHV FKROHVWHURO SKRVSKROLSLGV DQG DSROLSRSURWHLQV EHIRUH EHLQJ UHOHDVHG DV FK\ORPLFURQV LQWR WKH EORRG WKURXJK WKH LQWHVWLQDO O\PSKDWLF YHVVHOV . ĮWRFRSKHURO LV UDSLGO\ UHPRYHG IURP WKH FK\ORPLFURQ UHPQDQWVwhen arriving the liver, where it becomes bound to a specific Į WRFRSKHUROWUDQVSRUWSURWHLQ773DQGLVLQFRUSRUDWHGLQWRKLJKGHQVLW\RUYHU\ODUJHGHQVLW\OLSRSURWHLQV+'/DQG