Coenzyme Q10 effects in neurodegenerative disease

Figures & data

Figure 1 Chemical structures of Coenzyme Q10 and its short-chain analog, idebenone.

Figure 2 CoQ10 in the mitochondrial electron transport chain. Coenzyme Q10 is a component of the electron transport chain located within the inner mitochondrial membrane, required for oxidative phosphorylation leading to ATP generation. It accepts electrons from complexes I(NADH-ubiquinone oxidoreductase) and II (succinate dehydrogenase) for transfer to complex III (ubiquinol-cytochrome c reductase). Idebenone is similarly involved in transfer of electrons from complex I to complex III.

Table 1 Studies of effects of CoQ10 on healthy animals and animal models of neurodegenerative disease

Model	Dose	Effect	Ref
Healthy rats	200 mg/kg daily × 1–2 months	30%–40% increase in cerebral mitochondrial CoQ concentrations	Matthews^Citation2
Huntington’s models
Malonate	200 mg/kg daily × 1–2 months	Prevented depletion of ATP Attenuated striatal lesions With nicotinamide, prevented increase in lactate on MRS	Beal^Citation29
3-NP	200 mg/kg daily × 1–2 months	Attenuation of striatal lesions by 90%	Matthews^Citation2
N171–82Q mice	500 mg/kg/day	Diminished motor symptoms No effect on survival Effect augmented by remacimide	Ferrante^Citation45
R6/R2 and N171–82Q transgenic mice	CoQ10 400 mg/kg/day ± remacemide 14 mg/kg/day	Prolonged survival (additive) Delayed motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions	Ferrante^Citation45
R6/R2 transgenic mice	1,000 to 20,000 mg/kg/day	Prolonged survival Improved motor performance Reduced weight loss Decrease in cerebral and striatal neuron atrophy, Htt aggregate accumulation	Smith^Citation8
R6/2 transgenic mice	CoQ10 (0.2%) and minocycline 5 mg/kg/day	Extended survival Improved motor performance Amerliorated weight loss and Htt aggregation (CoQ dominant effect)	Stack^Citation71
3-NP	CoQ10 (1%) and creatine (2%) × two weeks	Reduced striatal lesion volumes (additive)	Yang^Citation72
R6/2 transgenic mice	CoQ10 (1%) and creatine (2%) × 9–11 weeks	Improved motor performance (additive) Extended survival (additive)	Yang^Citation72
Parkinson’s models
MPTP	CoQ10 200 mg/kg/day × five weeks	Protected against: Striatal dopamine depletion Loss of TH-IR neurons in the SNpc	Beal^Citation27
MPTP	CoQ10 1600 mg/kg × 3.5 months	Protected against: Dopamine depletion Loss of TH-IR neurons in the SNpc Development of α-synuclein aggregates in SNpc	Cleren^Citation68
MPTP	CoQ10 (1%) and creatine (2%) × 5 weeks	Protected against: Dopamine depletion in the striatum (additive) Loss of tyrosine hydroxylase neurons in SNpc (additive) Lipid peroxidation α-synuclein aggregates in SNpc	Yang^Citation72
ALS models
G93 A SOD1 transgenic mouse	200 mg/kg daily from day 50 until end-stage disease	Significantly increased median survival by 4.4% (six days)	Matthews^Citation2
Alzheimer models
Aged APP, PS1, APP/PS1 transgenic mice	2,400 mg/kg/day × 60 days	Attenuated brain atrophy as assessed by MRI in vivo	Li^Citation74
Aged PS1 transgenic mouse	1,200 mg/day × 60 days	Partially reduced Aβ overproduction and intracellular cortical deposits Attenuation of elevated malondialdehyde levels and downregulated SOD	Yang^Citation73
TG19959 mice	0.4% in diet	Protected against plaques Protected against memory loss as assessed by Morris water maze task	Kipiani^Citation75

Abbreviations: mg, milligram; kg, kilogram; CoQ, coenzyme Q; CoQ10, coenzyme Q10; ATP, adenosine triphosphate; MRS, magnetic resonance spectroscopy; 3-NP, 3-nitroproprionic acid; Htt, huntingtin; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; TH-IR, tyrosine hydroxylase-immunoreactive; SNpc, substantia nigra pars compacta; SOD, superoxide dismutase; Aβ, β-amyloid; APP, amyloid precursor protein; PS1, presenilin 1; MRI, magnetic resonance imaging.

Table 2 Clinical trials of CoQ10 in neurodegenerative disease

Study type	n	Dose	Effect	P value	Ref
Parkinson’s
Open label	10	200 mg/day × three months	No significant effect on UPDRS and motor testing	–	Strijks^Citation4
Open label Phase I	15	400, 600, and 800 mg/day × one month	No change in UPDRS or video Increase in plasma CoQ10 levels relative to controls Trend towards increased complex I activity	<0.05	Shults^Citation77
Phase II (QE2) randomized, double-blind, placebo-controlled	80	300, 600, and 1200 mg/day, up to 16 months with Vitamin E 1200 IU/day	44% less functional decline, most pronounced in ADLs (part II UPDRS) Met significance in 1,200 mg dose group (P = 0.04) Increased activity of electron transport chain complexes I & III Did not decrease time to levodopa	0.09	Shults^Citation78
				0.04
				0.04
Placebo-controlled, double-blind	28	360 mg/day × four weeks	Mild but significant improvement in UPDRS No improvement of motor symptoms Significant improvement in performance on color visual testing	0.01	Muller^Citation81
				0.008
Open label	12	1,000 mg/day × three months, then 1,500 mg/day × three months	Minor but statistically significant beneficial effect on motor performance with 1,500 mg versus placebo	0.004	Horstink^Citation82
Randomized, placebo-controlled, double-blind, Levodopa-stratified	106	100 mg three times/day × three months	No significant change in UPDRS – no symptomatic effects	–	Storch^Citation80
Open label	17	1,200 to 3,000 mg/day over eight weeks	Plateau of plasma levels at 2,400 mg/day No change in video exam or UPDRS	–	Shults^Citation19
Randomized, Double-blind	71	2,400 mg/day	Did not meet futility criteria	0.48	NINDS-PET^Citation79
Huntington’s
Open label	10	600–1,200 mg/day × six months	No significant effect on clinical scores	–	Feigin^Citation83
Open label	18	360 mg/day for >2 months	Ameliorated cerebral cortex lactate levels seen on MRS	<0.001	Koroshetz^Citation84
Randomized, placebo-controlled, double-blind (CARE-HD)	174	300 mg twice daily, × 30 months, also in combination with remacimide	Trend toward lessened decline in total functional capacity of HD rating scale, after one year	0.15	HSG^Citation86
Friedreich’s ataxia
Open label	10	400 mg/day with Vitamin E 2,100 IU/day, × 47 months	No improvement or progression in neurologic evaluation at six months At 47 months, compared to cross-sectional data, slowed progression of total ICARS and kinetic scores for seven patients	<0.01	Hart^Citation89
Double-blind, randomized	50	30 mg/day alone vs 600 mg/day with Vitamin E 2100 IU	49% with improved ICARS compared to cross-sectional data	–	Cooper^Citation31
ALS
Open label, placebo-controlled	31	Up to 3000 mg/day for eight months	Plateau at 2400 mg/day No adverse effects at 3,000 mg/day		Ferrante^Citation92
Phase II trial Futility study	185	1,800 mg/day vs 2,700 mg/day for nine months	No significant differences between CoQ10 and placebo Insufficient promise to warrant phase III testing	–	Kaufmann^Citation93
Progressive supranuclear palsy
Phase II trial	21	5 mg/kg/day × six weeks	Ratio of high-energy to low-energy phosphates increased in occipital lobe, trend in basal ganglia Significant mild improvement in PSP rating scale and frontal assessment battery		Stamelou^Citation91

Abbreviations: mg, milligrams; kg, kilograms; UPDRS, Unified Parkinson’s Disease Rating Scale; CoQ10, coenzyme Q10; IU, international units; ADLs, activities of daily living; NINDS, National institute of Neurological Disorders and Stroke; NET-PD, Neuroprotection Exploratory Trials in Parkinson’s Disease; HD, Huntington’s disease; HSG, Huntington’s Study Group; ICARS, international Cooperative Ataxia rating Scale; PSP, progressive supranuclear palsy; MRS,.

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