Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.
Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 μg/mL (baseline, n = 28), 5.59 ± 2.24 μg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 μg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 μg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 μg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.
University of Western Ontario, London, ON, Canada. chyson@uwo.ca
Hyson
H Christopher
HC
Kieburtz
Karl
K
Shoulson
Ira
I
McDermott
Michael
M
Ravina
Bernard
B
de Blieck
Elisabeth A
EA
Cudkowicz
Merit E
ME
Ferrante
Robert J
RJ
Como
Peter
P
Frank
Sam
S
Zimmerman
Carol
C
Cudkowicz
Merit E
ME
Ferrante
Kimberly
K
Newhall
Kristyn
K
Jennings
Danna
D
Kelsey
Tammie
T
Walker
Francis
F
Hunt
Vicki
V
Daigneault
Susan
S
Goldstein
Michele
M
Weber
Joseph
J
Watts
Arthur
A
Beal
M Flint
MF
Browne
Susan E
SE
Metakis
Linda J
LJ
D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome; D014451:Ubiquinone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014451:Ubiquinone; C024989:coenzyme Q10