Coenzyme Q10 appears to slow the affects of Parkinson's Disease, degenerative neurological disorder for which no treatment has been shown to slow the progression.[10] In a national clinical trial with 80 Parkinson's disease patients who did not require treatment for their disability, those patients who were given CoQ10 supplements showed signs that the disease was progressing less rapidly than would have been expected. The greatest benefit was seen everyday activities of the Parkinson's Disease patients such as feeding, dressing, bathing and walking. Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage of the supplement.

American Medical Association's Archives of Neurology's October 15, 2002 issue published the study that was conducted at ten sites by the Parkinson Study Group, under the direction of investigator Clifford Shults, M.D. Professor of Neurosciences, University of California, San Diego School of Medicine.

Dr. Shults explained that CoQ10 is a potent antioxidant and that mitochondria produce the energy containing molecules that it plays a key role in supplying energy to chemical reactions in cells. Dr. Shults and other researchers noticed that patients with Parkinson's Disease have low levels of CoQ10 in their mitochondria.

According to Richard Haas, M.D., Professor of Neurosciences at the University of California, San Deigo, "Coenzyme Q10 plays a crucial role in normal mitochondrial function both as a component of the electron transport chain which makes cellular energy and as a molecule with antioxidant and pro-oxidant properties".

Here is an article published on October 15, 2002, on the National Parkinson's Foundation website:

"CoQ10 was safe and well tolerated at doses of up to 1200 mg/day. Less disability developed in subjects on CoQ10 than in those on placebo, and the benefit was greatest in people receiving the highest dosage. CoQ10 appears to slow the progression of PD, but the results need to be confirmed in a larger study. Based on studies researchers suggest 1200mg of CoQ10 daily to slow the progression of Parkinson's Disease. To date, no toxicities have been reported. Occasional mild stomach upset may occur. Taking CoQ10 with meals usually alleviates this symptom."

(The abstract from the Archives of Neurology Vol. 59, October 2002 was modified by Dr Abe Lieberman)

Bioenergetic approaches for neuroprotection in Parkinson's disease.

Ann Neurol 2003;53(3 Suppl 1):S39-48

Beal MF.

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY.

There is considerable evidence suggesting that mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Parkinson's disease (PD). This possibility has been strengthened by recent studies in animal models, which have shown that a selective inhibitor of complex I of the electron transport gene can produce an animal model that closely mimics both the biochemical and histopathological findings of PD. Several agents are available that can modulate cellular energy metabolism and that may exert antioxidative effects. There is substantial evidence that mitochondria are a major source of free radicals within the cell. These appear to be produced at both the iron-sulfur clusters of complex I as well as the ubiquinone site. Agents that have shown to be beneficial in animal models of PD include creatine, coenzyme Q(10), Ginkgo biloba, nicotinamide, and acetyl-L-carnitine. Creatine has been shown to be effective in several animal models of neurodegenerative diseases and currently is being evaluated in early stage trials in PD. Similarly, coenzyme Q(10) is also effective in animal models and has shown promising effects both in clinical trials of PD as well as in clinical trials in Huntington's disease and Friedreich's ataxia. Many other agents show good human tolerability. These agents therefore are promising candidates for further study as neuroprotective agents in PD. Ann Neurol 2003;53 (suppl 3):S39-S48

PMID: 12666097 [PubMed - in process]

Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.

Arch Neurol. 2002 Oct;59(10):1523.

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group.

Department of Neurosciences, Mail Code 0662, University of California-San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0662, USA. cshults@ucsd.edu

BACKGROUND: Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. OBJECTIVE: To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. DESIGN: Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial. SETTING: Academic movement disorders clinics. PATIENTS: Eighty subjects with early PD who did not require treatment for their disability. INTERVENTIONS: Random assignment to placebo or coenzyme Q10 at dosages of 300, 600, or 1200 mg/d. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up 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. RESULTS: 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 1200-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.09, which met our 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 1200-mg/d and placebo groups was significant (P =.04). CONCLUSIONS: Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.

PMID: 12374491 [PubMed - indexed for MEDLINE]

Coenzyme Q10 as a possible treatment for neurodegenerative diseases.

Free Radic Res 2002 Apr;36(4):455-60

Beal MF.

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, NY 10021, USA. fbeal@mail.med.cornell.edu

Coenzyme Q10 (CoQ10) is an essential cofactor of the electron transport gene as well as an important antioxidant, which is particularly effective within mitochondria. A number of prior studies have shown that it can exert efficacy in treating patients with known mitochondrial disorders. We investigated the potential usefulness of coenzyme Q10 in animal models of Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). It has been demonstrated that CoQ10 can protect against striatal lesions produced by the mitochondrial toxins malonate and 3-nitropropionic acid. These toxins have been utilized to model the striatal pathology, which occurs in HD. It also protects against 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice. CoQ10 significantly extended survival in a transgenic mouse model of ALS. CoQ10 can significantly extend survival, delay motor deficits and delay weight loss and attenuate the development of striatal atrophy in a transgenic mouse model of HD. In this mouse model, it showed additive efficacy when combined with the N-methyl-D-aspartate (NMDA) receptor antagonist, remacemide. CoQ10 is presently being studied as a potential treatment for early PD as well as in combination with remacemide as a potential treatment for HD.

PMID: 12069110 [PubMed - indexed for MEDLINE]

Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of parkinson's disease.

Biol Signals Recept 2001 May-Aug;10(3-4):224-53

Ebadi M, Govitrapong P, Sharma S, Muralikrishnan D, Shavali S, Pellett L, Schafer R, Albano C, Eken J.

Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, N.Dak. 58203-2817, USA. mebadi@medicine.nodak.edu

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson's disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson's disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the alpha-synuclein gene on chromosome 4 in the much more common sporadic, or 'idiopathic' form of Parkinson's disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson's disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson's disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of the brain, such as globus pallidus or cerebral cortex. Therefore, the specificity of mitochondrial impairment may play a role in the degeneration of nigrostriatal dopaminergic neurons. This view is supported by the fact that MPTP generating 1-methyl-4-phenylpyridine (MPP(+)) destroys dopaminergic neurons in the substantia nigra. Although the serum levels of CoQ10 is normal in patients with Parkinson's disease, CoQ10 is able to attenuate the MPTP-induced loss of striatal dopaminergic neurons.

PMID: 11351130 [PubMed - indexed for MEDLINE]

Parkinson's disease as multifactorial oxidative neurodegeneration: implications for integrative management.

Altern Med Rev 2000 Dec;5(6):502-29

Kidd PM.

Parkinson's disease (PD) is the most common movement pathology, severely afflicting dopaminergic neurons within the substantia nigra (SN) along with non-dopaminergic, extra-nigral projection bundles that control circuits for sensory, associative, premotor, and motor pathways. Clinical, experimental, microanatomic, and biochemical evidence suggests PD involves multifactorial, oxidative neurodegeneration, and that levodopa therapy adds to the oxidative burden. The SN is uniquely vulnerable to oxidative damage, having high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate. Oxidative phosphorylation abnormalities impair energetics in the SN mitochondria, also intensifying oxygen free radical generation. These pro-oxidative factors combine within the SN dopaminergic neurons to create extreme vulnerability to oxidative challenge. Epidemiologic studies and long-term tracking of victims of MPTP (1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine) poisoning, suggest oxidative stress compounded by exogenous toxins may trigger the neurodegenerative progression of PD. Rational, integrative management of PD requires: (1) dietary revision, especially to lower calories; (2) rebalancing of essential fatty acid intake away from pro-inflammatory and toward anti-inflammatory prostaglandins; (3) aggressive repletion of glutathione and other nutrient antioxidants and cofactors; (4) energy nutrients acetyl L-carnitine, coenzyme Q10, NADH, and the membrane phospholipid phosphatidylserine (PS), (5) chelation as necessary for heavy metals; and (6) liver P450 detoxification support.

PMID: 11134975 [PubMed - indexed for MEDLINE]

Altered redox state of platelet coenzyme Q10 in Parkinson's disease.

J Neural Transm 2000;107(1):41-8

Gotz ME, Gerstner A, Harth R, Dirr A, Janetzky B, Kuhn W, Riederer P, Gerlach M.

Clinical Neurochemistry, Department of Psychiatry, University of Wurzburg, Federal Republic of Germany.

BACKGROUND: The reduced form of coenzyme Q10 (CoQ10) acts as a lipophilic antioxidant and participates in electron and proton transport of the respiratory chain in the inner mitochondrial membrane. An alteration in CoQ10 redox state may thus reflect a change in membrane electron transport and the effectiveness of defense against toxic reactive oxygen species such as hydrogen peroxide and superoxide. In Parkinson's disease alterations in the activities of complex I have been reported in substantia nigra and platelets. Deficiency of mitochondrial enzyme activities could affect electron transport which might be reflected by the platelet CoQ10 redox state. METHOD: We have determined concentrations of the reduced and oxidized forms of CoQ10 and the activity of monoamine oxidase B in platelets isolated from parkinsonian patients and age- and gender-matched controls. RESULTS: Platelet CoQ10 redox ratios (reduced CoQ10 to oxidized CoQ10) and the ratio of the reduced form, compared with total platelet CoQ10, were significantly decreased in de novo parkinsonian patients. Platelet CoQ10 redox ratios were further decreased by L-DOPA treatment (not significant), whilst selegiline treatment partially restored CoQ10 redox ratios. Monoamine oxidase activities in non-selegiline treated patients were similar to controls. INTERPRETATION: Our results either suggest an impairment of electron transport or a higher need for reduced forms of CoQ10 in the platelets of even de novo parkinsonian patients. However, the CoQ10 redox ratio was not correlated to disease severity, as determined by the Hoehn and Yahr PD disability classification, suggesting that this parameter may not be useful as a peripheral trait marker for the severity of PD but as an early state marker of PD.

PMID: 10809402 [PubMed - indexed for MEDLINE]

Serum levels of coenzyme Q10 in patients with Parkinson's disease.

J Neural Transm 2000;107(2):177-81

Jimenez-Jimenez FJ, Molina JA, de Bustos F, Garcia-Redondo A, Gomez-Escalonilla C, Martinez-Salio A, Berbel A, Camacho A, Zurdo M, Barcenilla B, Enriquez de Salamanca R, Arenas J.

Department of Medicine-Neurology, University of Alcala, Alcala de Henares, Madrid, Spain. Fjimenezj@meditex.es

We compared serum levels of coenzyme Q10 and the coenzyme Q10/cholesterol ratio in 33 patients with Parkinson's disease (PD) and 31 matched controls. The mean serum coenzyme Q10 levels did not differ significantly between the 2 study groups. Coenzyme Q10 levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale (UPDRS) or the Hoehn and Yahr staging in the PD group. The coenzyme Q10/cholesterol ratio had a significant correlation (although low) with duration of the disease (r = -0.46), total UPDRS score (r = -0.39), motor examination of the UPDRS (r = 0.45). These values were not influenced significantly by therapy with levodopa or dopamine agonists. The normality of serum coenzyme Q10 and coenzyme Q10/cholesterol ratio suggest that these values are not related with the risk for PD.

PMID: 10847558 [PubMed - indexed for MEDLINE]

A possible role of coenzyme Q10 in the etiology and treatment of Parkinson's disease.

Biofactors 1999;9(2-4):267-72

Shults CW, Haas RH, Beal MF.

Department of Neurosciences, University of California, San Diego, La Jolla 92093, USA.

Parkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q10 (CoQ10) than mitochondria from age/sex-matched controls. There was a strong correlation between the levels of CoQ10 and the activities of complexes I and II/III. Oral CoQ10 was found to protect the nigrostriatal dopaminergic system in one-year-old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ10 was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ10 may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients.

PMID: 10416040 [PubMed - indexed for MEDLINE]

Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases.

Biofactors 1999;9(2-4):261-6

Beal MF.

Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114, USA.

Coenzyme Q10 (CoQ10) is an essential cofactor of the electron transport chain as well as an important antioxidant. Previous studies have suggested that it may exert therapeutic effects in patients with known mitochondrial disorders. We investigated whether it can exert neuroprotective effects in a variety of animal models. We have demonstrated that CoQ10 can protect against striatal lesions produced by both malonate and 3-nitropropionic acid. It also protects against MPTP toxicity in mice. It extended survival in a transgenic mouse model of amyotrophic lateral sclerosis. We demonstrated that oral administration can increase plasma levels in patients with Parkinson's disease. Oral administration of CoQ10 significantly decreased elevated lactate levels in patients with Huntington's disease. These studies therefore raise the prospect that administration of CoQ10 may be useful for the treatment of neurodegenerative diseases.

PMID: 10416039 [PubMed - indexed for MEDLINE]

Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients.

Neurology 1998 Mar;50(3):793-5

Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH.

Department of Neurosciences, University of California, San Diego, La Jolla, USA.

We report a pilot study of three oral doses of coenzyme Q10 (CoQ10) (200 mg administered two, three, or four times per day for 1 month) in 15 subjects with Parkinson's disease. Oral CoQ10 caused a substantial increase in the plasma CoQ10 level. It was well tolerated, but at the highest dose (200 mg four times per day) mild, transient changes in the urine were noted. CoQ10 did not change the mean score on the motor portion of the Unified Parkinson's Disease Rating Scale. There was a trend toward an increase in complex I activity in the subjects.

PMID: 9521279 [PubMed - indexed for MEDLINE]

Q10 therapy in patients with idiopathic Parkinson's disease.

Mol Aspects Med 1997;18 Suppl:S237-40

Strijks E, Kremer HP, Horstink MW.

Department of Neurology, University Hospital Nijmegen, The Netherlands.

A 3-month open-label trial was performed to evaluate the efficacy of 200 mg Q10 daily in 10 patients with Parkinson's disease. Motor performance was assessed with UPDRS and motor tests. There was no significant effect on the clinical ratings.

PMID: 9266528 [PubMed - indexed for MEDLINE]

Mitochondrial medicine--molecular pathology of defective oxidative phosphorylation.

Ann Clin Lab Sci 2001 Jan;31(1):25-67

Fosslien E.

Department of Pathology, College of Medicine, University of Illinois at Chicago, 60612, USA. efosslie@uic.edu

Different tissues display distinct sensitivities to defective mitochondrial oxidative phosphorylation (OXPHOS). Tissues highly dependent on oxygen such as the cardiac muscle, skeletal and smooth muscle, the central and peripheral nervous system, the kidney, and the insulin-producing pancreatic beta-cell are especially susceptible to defective OXPHOS. There is evidence that defective OXPHOS plays an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. Defective OXPHOS may be caused by abnormal mitochondrial biosynthesis due to inherited or acquired mutations in the nuclear (n) or mitochondrial (mt) deoxyribonucleic acid (DNA). For instance, the presence of a mutation of the mtDNA in the pancreatic beta-cell impairs adenosine triphosphate (ATP) generation and insulin synthesis. The nuclear genome controls mitochondrial biosynthesis, but mtDNA has a much higher mutation rate than nDNA because it lacks histones and is exposed to the radical oxygen species (ROS) generated by the electron transport chain, and the mtDNA repair system is limited. Defective OXPHOS may be caused by insufficient fuel supply, by defective electron transport chain enzymes (Complexes I - IV), lack of the electron carrier coenzyme Q10, lack of oxygen due to ischemia or anemia, or excessive membrane leakage, resulting in insufficient mitochondrial inner membrane potential for ATP synthesis by the F0F1-ATPase. Human tissues can counteract OXPHOS defects by stimulating mitochondrial biosynthesis; however, above a certain threshold the lack of ATP causes cell death. Many agents affect OXPHOS. Several nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit or uncouple OXPHOS and induce the 'topical' phase of gastrointestinal ulcer formation. Uncoupled mitochondria reduce cell viability. The Helicobacter pylori induces uncoupling. The uncoupling that opens the membrane pores can activate apoptosis. Cholic acid in experimental atherogenic diets inhibits Complex IV, cocaine inhibits Complex I, the poliovirus inhibits Complex II, ceramide inhibits Complex III, azide, cyanide, chloroform, and methamphetamine inhibit Complex IV. Ethanol abuse and antiviral nucleoside analogue therapy inhibit mtDNA replication. By contrast, melatonin stimulates Complexes I and IV and Gingko biloba stimulates Complexes I and III. Oral Q10 supplementation is effective in treating cardiomyopathies and in restoring plasma levels reduced by the statin type of cholesterol-lowering drugs.

PMID: 11314862 [PubMed - indexed for MEDLINE]

Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects.

Ann Neurol 1997 Aug;42(2):261-4

Shults CW, Haas RH, Passov D, Beal MF.

Neurology Service, Veterans Affairs Medical Center, San Diego, CA 92161, USA.

The activities of complex I and complex II/III in platelet mitochondria are reduced in patients with early, untreated Parkinson's disease. Coenzyme Q10 is the electron acceptor for complex I and complex II. We found that the level of coenzyme Q10 was significantly lower in mitochondria from parkinsonian patients than in mitochondria from age- and sex-matched control subjects and that the levels of coenzyme Q10 and the activities of complex I and complex II/III were significantly correlated.

PMID: 9266740 [PubMed - indexed for MEDLINE]