A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis.
OBJECTIVE
Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS.


METHODS
Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses.


RESULTS
Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).


CONCLUSIONS
We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation.


METHODS
This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
Department of Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia. Mark.Stein@mh.org.au
M S
MS
Stein
Y
Y
Liu
O M
OM
Gray
J E
JE
Baker
S C
SC
Kolbe
M R
MR
Ditchfield
G F
GF
Egan
P J
PJ
Mitchell
L C
LC
Harrison
H
H
Butzkueven
T J
TJ
Kilpatrick
D015652:25-Hydroxyvitamin D 2 / Q000097:blood / Q000627:therapeutic use*; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000097:blood; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011863:Radioimmunoassay; D013997:Time Factors; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use*
D014815:Vitamins; D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol; D002118:Calcium