February 3, 2016

Reconsidering Coenzyme Q10 in Parkinson's Disease

Weighing the cost versus the benefit
A recent study stirs up lingering questions about whether CoQ10 is worth recommending for Parkinson’s disease, and, if so, which form is best.


Yoritaka A, Kawajiri S, Yamamoto Y, et al. Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease. Parkinsonism Relat Disord. 2015;21(8):911-916. 


Randomized, double-blind, placebo-controlled, parallel-group pilot trials


Japanese patients with a current diagnosis of Parkinson’s disease (PD). Participants were divided into 2 parallel groups. Group A included those on levodopa who experience “wearing off” effects (ie, early breakthrough of PD symptoms before the next scheduled dose of medication). Group B included those with an early diagnosis but not yet taking levodopa, although other medications were allowed. At trial end points, group A had 14 evaluable participants in the intervention group and 12 in the placebo. Group B had 14 participants in the intervention group and 8 in the placebo.


Reduced coenzyme Q10 (ubiquinol-10, 300 mg/day) or placebo taken as 3 capsules twice daily. Each capsule contained 50 mg ubiquinol-10, 68.31 mg glycerin fatty acid ester, 0.3 mg lecithin, 154.39 mg rapeseed oil, and 22 mg beeswax. Placebo contained all but the 50 mg ubiquinol. Group A took ubiquinol-10 or placebo for 48 weeks total and Group B for 96 weeks total.

Outcome Measures

Total Unified Parkinson’s Disease Rating Scale (UPDRS) was used to track functional deficits of PD. Assessment was done at baseline and at weeks 8, 24, and 48 and 8 weeks after stopping the intervention for group A. Group A participants were assessed in both their “on” and “off” phases. Group B was assessed at baseline and weeks 8, 24, 48, and 96 and 8 weeks after the intervention ceased.

Key Findings

Group A: UPDRS scores decreased (-4.2 +-8.2) for the ubiquinol-10 group and increased (2.9=-8.9) for the placebo group. This difference was statistically significant (P<0.05). There were no significant changes in the time of “on” and “off” phases. There were significant differences in subscores for finger and hand movements (P<0.05). However, there were no significant differences in tremor, rigidity, foot tap, arising from a chair, posture, gait, or akinesia. Improvements were not maintained at 8 weeks after ceasing the ubiquinol-10.
Group B: There were no significant differences in total UPDRS scores between intervention and placebo arms. There were no significant changes in any subscores at any time point, nor at the 8-week post-intervention assessment.
Supplementation with ubiquinol-10 raised levels of circulating CoQ10 approximately 10-fold in both groups. Levels of CoQ10 did not correlate with any symptom changes in either group.

Practice Implications

PD is a progressive disease, and established drug treatments can forestall but not halt the disease process. In 2002, a small study, the QE2 trial, elicited excitement by suggesting that taking 1,200 mg/day of CoQ10 (as ubiquinone-10 + alpha tocopherol) may benefit those with early PD.1 Unfortunately, a similarly designed phase III trial (QE3) with more than 600 participants taking up to 2,400 mg/day of ubiquinone + alpha tocopherol was stopped early due to lack of benefit (median duration on study, 10.4 months). The results of QE3 were published in 2014.2 In the interim between the QE2 and QE3 studies, smaller trials of ubiquinone-10 also failed to show any benefit in early PD.3,4
The current pilot study is the first to use the reduced form of CoQ10 (ubiquinol-10) in patients with PD. It suggests that ubiquinol-10 may lessen some of the symptoms of PD in those with “wearing off” on levodopa. However, it failed to show any improvement in those with an early diagnosis not yet taking levodopa. While this study is too small to draw definitive clinical guidance, it stirs up lingering questions regarding whether CoQ10 is worth recommending and, if so, which form is best.
The pathogenesis of PD has long been suspected to be due to impairment/loss of energy production in the mitochondrial respiratory chain in general, and complex I in particular.5 Early research implicated free radical damage as the cause for this, since it is always present and ongoing in the neurons of the substantia nigra in PD. Free radical damage to neurons is clearly involved in neurodegeneration, but whether free radicals are causative or associative remains debatable.6
This more complicated pathophysiology in PD may explain why simply increasing CoQ10 is not enough to measurably slow the progression of disease.
The rationale behind using CoQ10 in PD has been to support complex I energy production and to act as an antioxidant to prevent damage in the first place. This seemed logical, particularly when coupled with ongoing clinical data showing a deficiency of CoQ10 is common in those with PD.7 We now know the dysfunction of the mitochondria in neurodegenerative diseases is much more complicated than previously appreciated. Recent data suggests dysfunction of the mitochondria is a culmination of many possible cellular aberrations, including mutations in mitochondrial DNA (mtDNA), mutations in nuclear genes regulating mtDNA or mitochondrial proteins, and misfolding of key mitochondrial proteins (ie, synuclein in PD).8,9 This more complicated pathophysiology in PD may explain why simply increasing CoQ10 is not enough to measurably slow the progression of disease.
The current study suggests that ubiquinol-10 may have some beneficial effect in those already taking levodopa. However, the results for those with early PD are in keeping with the majority of prior findings for ubiquinone-10. Namely, high-dose CoQ10 does not slow progression of disease. Larger trials are needed to discern whether the findings in this current pilot study are replicable for those with “wearing off” of their levodopa effects.
Ubinquinol-10 is reduced CoQ10 and ubiqinone-10 is the oxidized form. Inter-conversion between these molecules is readily achieved through redox flux. That said, 95% of circulating CoQ10 is in the reduced state, ubiquinol-10, regardless of which form is given orally.10 The oral absorption of ubiquinol-10 does appear to be superior to ubiquinone-10 by 3- to 4-fold.11 However, commercially available supplements compensate for this by providing ubiquinol in lower-dose forms, usually 50-100 mg/capsule. The study currently reviewed here also compensated for this difference by using only 300 mg/day of ubiquinol-10 versus up to 2,400 mg/day of ubiquinone-10 that was used other PD studies.
From a practical perspective, the cost of high-dose CoQ10, as either ubiquinol or ubiquinone, is difficult to justify for those with early PD given the evidence to date.  A dose that will ensure the patient is not deficient is prudent given the likelihood of deficiency with PD. Whether the ideal form is ubiquinol or ubiquinone is still an open question, since either form will result in increased ubiquinol in the plasma.

Categorized Under


  1. Shults CW. Effects of coenzyme Q10 in early parkinson disease. Arch Neurol. 2002;59(10):1541.
  2. Beal MF, Oakes D, Shoulson I, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-552. 
  3. Snow BJ, Rolfe FL, Lockhart MM, et al. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson’s disease. Mov Disord. 2010;25(11):1670-1674. 
  4. NINDS-NET PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007;68(1):20-28. 
  5. Schapira A. Mitochondrial complex i deficiency in parkinson’s disease. Lancet. 1989;333(8649):1269. 
  6. Jenner P. Oxidative stress in Parkinson’s disease. Ann Neurol. 2003;53 Suppl 3:S26-S36; discussion S36-S38. 
  7. Mischley LK, Allen J, Bradley R. Coenzyme Q10 deficiency in patients with Parkinson’s disease. J Neurol Sci. 2012;318(1-2):72-75.
  8. Schapira AH V, Gegg M. Mitochondrial contribution to Parkinson’s disease pathogenesis. Parkinsons Dis. 2011;2011:159160. 
  9. Valera E, Masliah E. Therapeutic approaches in Parkinson’s disease and related disorders. J Neurochem. 2016 Jan 9. doi: 10.1111/jnc.13529. [Epub ahead of print] 
  10. Franke AA, Morrison CM, Bakke JL, Custer LJ, Li X, Cooney R V. Coenzyme Q10 in human blood: native levels and determinants of oxidation during processing and storage. Free Radic Biol Med. 2010;48(12):1610-1617. 
  11. Bhagavan HN, Chopra RK. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion. 2007;7 Suppl:S78-S88.