Coenzyme Q10 and Parkinson’s Disease
Source: Shults CW, et al. Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline. Arch Neurol 2002;59: 1541-1550.
Parkinson’s disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. To determine whether a range of dosages of coenzyme Q10 (CoQ10) is safe and well tolerated and could slow the functional decline in PD, the authors conducted a multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial.
Working in academic movement disorders clinics, the authors recruited 80 subjects with early PD in 10 sites who did not require treatment for their disability, and randomly assigned them to placebo or CoQ10 at dosages of 300, 600, or 1,200 mg/d. The subjects had all three cardinal features of PD (resting tremor, bradykinesia, and rigidity), which had to be asymmetrical. The diagnosis of PD was made within the previous five years in men or in women 30 years or older.
Subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and one-, four-, eight-, 12-, and 16-month visits. They were followed for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit.
The primary statistical analyses were performed according to the intention-to-treat principle. The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300 mg/d group, +10.82 for the 600 mg/d group, and +6.69 for the 1,200 mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was 0.09, which met the prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1,200 mg/d and placebo groups was significant (P = 0.04).
The authors concluded that CoQ10 was safe and well tolerated at dosages of up to 1,200 mg/d. Less disability developed in subjects assigned to CoQ10 than in those assigned to placebo; the benefit was greatest in subjects receiving the highest dosage. CoQ10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.
Approximately 1% of American adults older than age 65 has PD. Al-though medication can slow the symptoms, no medication or procedure of which I’m aware actually slows its progression. Except, perhaps, CoQ10.
This small study, funded by the National Institute of Neurological Disorders and Stroke, and centered at the University of California-San Diego, suggests that CoQ10 may actually slow progression. The work was designed as a dosage-ranging study, and attempted to identify a trend toward efficacy, instead of to demonstrate effectiveness or efficacy.
CoQ10 is a potent antioxidant, and is normally present in mitochondria; PD patients have reduced levels of CoQ10 in their platelet mitochondria, and have lower serum levels of CoQ10 than age-comparable patients with stroke.
Here, CoQ10 was administered in the form of a maple nut wafer, four times daily. The drop-out rate was low, although the exclusion criteria for the study were substantial—off PD meds, no history of stroke, no PD from medication, and many more.
Remarkably, the subjects who took 1,200 mg/d—the highest dose—had 44% less decline in activities of daily living (plus mental function and movement) than did the subjects who took placebo.
Side effects were mild, and when mild events were excluded, three events were experienced by at least four subjects: viral infection, pharyngitis, and sinusitis. No adverse effects were significantly related to any dosage administration. High carbon dioxide levels (P = 0.01), which were significantly related to CoQ10 administration, were not judged to be clinically significant.
How might this work? The authors note, "The assay of NADH to cytochrome-c reductase activity, which relies on endogenous coenzyme Q10, demonstrated a significant increase in activity in subjects taking 1,200 mg/d of coenzyme Q10." The authors hypothesize that the same benefit occurred in the brain and that mitochondrial dysfunction, if corrected, does in fact improve PD symptoms.
Because the greatest effect was seen in activities of daily living, this work should make a real difference. It will be tested in broader scale, and rightly so.
In the short term, it seems prudent to recommend 1,200 mg daily of CoQ10 to patients at risk for PD, and who would not have been excluded from this study.