Parkinson's Disease (PD) is a progressive neurodegenerative disorder typified by bradykinesia, tremor, muscle rigidity and postural instability and is physiologically characterized by the presence of Lewy bodies and a decrease of dopaminergic neurons in the substantia nigra pars compacta. According to the Parkinson Society of Canada, approximately 100,000 Canadians currently suffer from this debilitating disorder.
Because loss of dopamine is believed to account for the impaired nerve and muscle control observed in PD, levodopa tends to be the prescribed treatment of choice. While the causes of PD have yet to be fully elucidated, a defective mitochondrial electron-transport chain appears to play a role in the pathogenesis of sporadic PD. Decreased complex I levels may expose neurons to the damaging effects of oxygen-free radicals. The inhibition of complex I via 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been demonstrated to cause human parkinsonism, thus implicating the enzyme as vital to the elucidation of the molecular causes of PD. Previous research has indicated that coenzyme Q10, the electron acceptor for complexes I and II, may be orally administered to reduce dopamine loss, thus paving the way for the potential use of Q10 as an alternative treatment for early PD.
In a multicentre, randomized, doubleblind test, Shults et al. enrolled 80 early PD patients who had not used PD medication or antioxidants for at least 60 days in order to further evaluate the role of Q10 as a mediator of functional decline in PD patients.
Within one month of selection, patients were assessed clinically and blood samples were taken to ascertain Q10 levels in plasma and complex I activity in platelets. Following a baseline evaluation session, patients were randomly assigned to a Q10 dosage of either 300, 600 or 1200mg/day or to an equivalent placebo dosage. Patients were reassessed at one, four, eight, 12 and 16 months or until sufficient disability had occurred so as to necessitate levodopa treatment. The coenzyme was administered orally four times daily in the form of a wafer that contained vitamin E to function as a lipophilic carrier. Vitamin E was also present in the placebo wafer.
Dosage reductions were not required in any of the treatment groups, demonstrating the widespread tolerability of oral coenzyme Q10 therapy. Treatment efficacy was determined using the Unified Parkinson Disease Rating Scale (UPDRS), an assessment of mental, motor and activities of daily living (ADL) skills. The adjusted mean UPDRS changes were +8.81 for the 300mg/d group, +10.82 for the 600mg/d group, +6.69 for the 1200mg/d group and +11.99 in the placebo group. The primary analysis, a test for correlation between dosage and the mean change in UPDRS score, determined a p value of .09, signifying a linear trend according to prespecified criteria. The greatest reduction in UPDRS score was seen in the 1200mg/d group in the ADL realm of the UPDRS.
Mean plasma Q10 levels were significantly increased in all test groups. Mitochondrial assays demonstrated that complex I activity, which proceeds independently of endogenous coenzyme Q10, was unaffected in the various treatment groups. Conversely, the NADH to cytochrome-c reductase, which depends largely on endogenous Q10 levels, showed increased activity with increased Q10 dosage.
The findings of this clinical trial propose a role for orally administered Q10 in mitochondrial function. However, this role remains questionable with regards to PD, given that the results found in plasma have yet to be replicated in the brain. The authors suggest that high dosages of Q10 may be used in the treatment of neurological diseases which are characterized by defective complex I or complex II enzymes, such as PD and Huntington disease. The linear correlation between dose and decreased cognitive decline suggests that the effect of even higher Q10 dosages should be explored. Additionally, due to the complex interaction between genetic defects and environmental insult which likely contributes to PD, further investigation into the precise mechanism of dopamine loss is imperative for future PD alleviation.
- Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson Disease. Arch Neurol 2002;59:1541-50.