recentpub2

Below is a selection of some of the latest publications on CoQ10.

- Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM, Krisp A, Menke T, Schade-Brittinger C, Oertel WH, Höglinger GU. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov Disord. 2008 May 15;23(7):942-9.

Progressive supranuclear palsy is a serious neurodegenerative disorder for which no treatment is available. This double blind placebo-controlled study showed that CoQ10, when given as a liquid nanodispersion (5mg/kilo/day), determined an improvement in the energy metabolism of the occipital lobe, together with an amelioration of clinical scores.

- Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, Ricciardo-Lamonica G, Boscaro M, Lenzi A, Littarru G.P. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2008 Apr 5. [Epub ahead of print].

A brief comment to this paper is given on Page 2 of this newsletter (Andrology).

- Casarin A, Jimenez-Ortega JC, Trevisson E, Pertegato V, Doimo M, Ferrero-Gomez ML, Abbadi S, Artuch R, Quinzii C, Hirano M, Basso G, Ocaña CS, Navas P, Salviati L. Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis. Biochem Biophys Res Commun. 2008 Jul 18;372(1):35-9.

- Saiki R, Lunceford AL, Shi Y, Marbois B, King R, Pachuski J, Kawamukai M, Gasser DL, Clarke CF. Coenzyme Q10 Supplementation Rescues Renal Disease in Pdss2kd/kd mice with mutations in Prenyldiphosphate synthase subunit 2.

Am J Physiol Renal Physiol. 2008 Sep 10.

Mutations in the gene encoding subunit 2 of the enzyme responsible for the synthesis of coenzyme Q sidechain lead to lethal renal disease. Mouse kidneys bearing this mutation show serious deficiency in coenzyme Q content and dietary supplementation with CoQ10 provides a dramatic rescue of both proteinuria and interstitial nephritis.

- Montini G, Malaventura C, Salviati L. Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med. 2008 Jun 26;358(26):2849-50.

In this letter to the New England Journal of Medicine, the authors describe the results of longterm CoQ10 supplementation in 2 patients with CoQ10 deficiency caused by a homozygous mutation in the COQ2 gene. The first patient, in whom CoQ10 therapy was initiated at 22 months of age, improved his neurologic picture, but no change in renal function occurred, since advanced chronic renal failure had already developed. Patient 2, the sister of patient 1, who received a diagnosis of CoQ10 deficiency at 12 months of age, soon after developed a nephrotic syndrome with marked proteinuria, hypoalbuminemia and generalized edema. Treatment with oral CoQ10 at a dose of 30 mg/kg/body weight/day was associated with resolution of the nephrotic syndrome. After 50 months of therapy the patient’s renal function remains normal.

- Jin G, Kubo H, Kashiba M, Horinouchi R, Hasegawa M, Suzuki M, Sagawa T, Oizumi M, Fujisawa A, Tsukamoto H, Yoshimura S, Yamamoto Y. Saposin B is a human coenzyme Q10-binding/transfer protein. J Clin Biochem Nutr. 2008 Mar;42(2):167-74.

- Jin G, Horinouchi R, Sagawa T, Orimo N, Kubo H, Yoshimura S, Fujisawa A, Kashiba M, Yamamoto Y. Coenzyme Q10-Binding/Transfer Protein Saposin B also Binds gamma-Tocopherol.. J Clin Biochem Nutr. 2008 Sep;43(2):95-100.

These two papers shed light on the important issue of how CoQ10 and gamma tocopherol are transported intracellularly and in some biological fluids.

- Makhija N, Sendasgupta C, Kiran U, Lakshmy R, Hote MP, Choudhary SK, Airan B, Abraham R. The Role of Oral Coenzyme Q10 in Patients Undergoing Coronary Artery Bypass Graft Surgery. J Cardiothorac Vasc Anesth. 2008 Jun 5. [Epub ahead of print]

A group of patients undergoing coronary artery bypass surgery were treated with CoQ10, starting 7-10 days pre-operatively (150-180mg/day) until the morning of surgery. A corresponding group received placebo. The CoQ10 treated group had significantly fewer reperfusion arrhythmias, lower total inotropic requirement, mediastinal drainage blood requirement, and shorter hospitalization compared to the control group.

- Suzuki T, Nozawa T, Sobajima M, Igarashi N, Matsuki A, Fujii N, Inoue H. Atorvastatin-induced changes in plasma coenzyme Q10 and brain natriuretic peptide in patients with coronary artery disease. Int Heart J. 2008 Jul;49(4):423-33.

This paper shows that plasma levels of CoQ10 were lower in patients who had high levels of brain natriuretic peptide (BNP), whose elevation is related to deterioration of left ventricular function. Treatment with atorvastatin reduced plasma CoQ10 (and cholesterol) and the reduction in plasma CoQ10 also resulted in increased plasma BNP levels. The authors conclude that chronic treatment with atorvastatin may deteriorate ventricular function, in patients with stable coronary artery disease, if it is accompanied by a marked reduction in plasma CoQ10 levels.

- Chatzizisis YS, Vaklavas C, Giannoglou GD. Coenzyme Q10 depletion: etiopathogenic or predisposing factor in statin

associated myopathy? Am J Cardiol. 2008 Apr 1;101(7):1071.

- Harinstein ME, Berliner JI, Shah SJ, Taegtmeyer H, Gheorghiade M. Normalization of ejection fraction and resolution of symptoms in chronic severe heart failure is possible with modern medical therapy: clinical observations in

11 patients. Am J Ther. 2008 May-Jun;15(3):206-13.

The paper is interesting because of the dramatic improvement in New York Heart Association heart failure classification from IV to I in 9 of the 11 patients. This dramatic clinical improvement along with the remarkable improvement in ejection fraction from 10%-35% up to a normal of 55%-70% in all 11 patients would be highly unusual with standard medical therapy alone. It should be noted that 9 of these 11 cases were on statin drug therapy and it is certain that most of these patients would have been very low in coenzyme Q10 and therefore more likely to have a dramatic improvement with supplemental coenzyme Q10. The dose of coenzyme Q10 is only mentioned in one patient who was on 100mg/day as a maintenance dose after clinical improvement. The authors make a very good point in noting that all 11 patients had evidence of weak but still viable myocardium without evidence of scarring which has the greatest potential for improvement.

- Chew GT, Watts GF, Davis TM, Stuckey BG, Beilin LJ, Thompson PL, Burke V, Currie PJ. Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care. 2008 Aug;31(8):1502-9. Epub 2008 May 16.

This paper shows that CoQ10 and fenofibrate independently lower systolic and diastolic blood pressure in Type 2 diabetic subjects.

- Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM. Coenzyme Q10. An independent predictor of mortality in chronic heart failure.

J Am Coll Cardiol. 2008 Vol 52, No.18, [Epub ahead of print]

This is the first observational study where CoQ10 plasma levels were related to the outcome of heart failure. Multivariable analysis indicated that lower CoQ10 and lower CoQ10/lipid ratio predicted poorer survival. Moreover CoQ10 was an independent predictor of survival and the strength of association between CoQ10 and mortality was greater than that observed for NT-proBNP. The authors conclude that “it is therefore plausible that CoQ10 deficiency might be an important pathogenetic mechanism associated with worse outcomes in chronic heart failure”.

- Molyneux SL, Young JM, Florkowski CM, Lever M, George PM. Coenzyme Q10: is there a clinical role and a case for measurement? Clin Biochem Rev. 2008 May;29(2):71-82.

This is a review article mainly based on the predictive values of CoQ10 plasma levels related to the article by the same authors mentioned above, but it also extensively discusses methodological aspects of CoQ10 analysis and factors affecting plasma CoQ10 concentration. Besides taking into account several inborn and acquired CoQ10 deficiencies the paper extensively discusses biological variations and the significant changes in plasma CoQ10 levels.

- Juan YS, Chuang SM, Mannikarottu A, Huang CH, Li S, Schuler C, Levin RM. Coenzyme Q10 diminishes ischemia-reperfusion induced apoptosis and nerve injury in rabbit urinary bladder. Neurourol Urodyn. 2008 Oct 6. [Epub ahead of print]

- Juan YS, Levin RM, Chuang SM, Hydery T, Li S, Kogan B, Schuler C, Huang CH, Mannikarottu A. The Beneficial Effect of Coenzyme Q10 and Lipoic Acid on Obstructive Bladder

Dysfunction in the Rabbit. J Urol. 2008 Sep 18. [Epub ahead of print]

The first of these two papers shows that CoQ10 supplementation alone provides significant bladder protection against ischemia/reperfusion injury mainly by protecting against damage to cholinergic innervation.

In the second one, treatment with CoQ10 plus alphalipoic acid significantly restored contractile responses after the animals had undergone surgical partial bladder obstruction.

- Othman AA, Shoheib ZS, Abdel-Aleem GA, Shareef MM.

Experimental schistosomal hepatitis: protective effect of coenzyme-Q10 against the state of oxidative stress.

Exp Parasitol. 2008 Oct;120(2):147-55. Epub 2008 Jul 1.

This is the first paper describing a protective effect of Coenzyme Q10 in experimental schistosomiasis. Administration of CoQ10, for 12 weeks, to infected animals had a normalizing effect on antioxidant parameters and oxidative stress markers. Histopathological findings were also ameliorated by CoQ10 supplementation, which very significantly decreased the activation of stellate cells, whose role is well acknowledged in the process leading to liver fibrosis.

- Rodríguez-Acuña R, Brenne E, Lacoste F. Determination of coenzyme Q10 and Q9 in vegetable oils. J Agric Food Chem. 2008 Aug 13;56(15):6241-5. Epub 2008 Jul 11.

- Nakajima Y, Inokuchi Y, Nishi M, Shimazawa M, Otsubo K, Hara H. Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo. Brain Res. 2008 Aug 21;1226:226-33. Epub 2008 Jun 18.

This paper highlight the combined antioxidant effect of CoQ10 and vitamin E in retinal cells and its possible consequences on neuroprotection.

- Gassió R, Artuch R, Vilaseca MA, Fusté E, Colome R, Campistol J. Cognitive functions and the antioxidant system in phenylketonuric patients. Neuropsychology. 2008 Jul;22(4):426-31.

- Bélanger MC, Mirault ME, Dewailly E, Berthiaume L, Julien P. Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik. Metabolism. 2008 Jul;57(7):927-33.

- Laguna TA, Sontag MK, Osberg I, Wagener JS, Accurso FJ, Sokol RJ. Decreased total serum coenzyme-Q10 concentrations: a longitudinal study in children with cystic fibrosis.

J Pediatr. 2008 Sep;153(3):402-7. Epub 2008 Jun 2.

This paper demonstrates that most pediatric patients with cystic fibrosis (CF) have low total serum CoQ10 levels and these values are particularly low in PI patients, the ones with two known “severe” mutations. Furthermore there was an association between low CoQ10 levels and P aeruginosa colonization in younger patients with CF. Besides the possibile clinical implications of low CoQ10 values in CF patients, this paper also highlights the fact that intestinal absorption of CoQ10 and/or vitamins and cofactors needed for its biosynthesis is relevant for the body’s CoQ10 status.

- Sakata T, Furuya R, Shimazu T, Odamaki M, Ohkawa S, Kumagai H. Coenzyme Q10 administration suppresses both oxidative and antioxidative markers in hemodialysis patients. Blood Purif. 2008;26(4):371-8. Epub 2008 May 29.

This study demonstrated the potential of CoQ10 in reducing oxidative stress as assessed by advanced oxidation protein products (AOPP) and the redox status of CoQ10. Total plasma antioxidant capacity was also decreased following CoQ10 treatment and possibile explanations are discussed.

- Kitano M, Watanabe D, Oda S, Kubo H, Kishida H, Fujii K, Kitahara M, Hosoe K. Subchronic oral toxicity of ubiquinol in rats and dogs. Int J Toxicol. 2008 Mar-Apr;27(2):189-215.

Ubiquinol formulations are becoming more and more common. This extensive study was aimed to assess the safety of ubiquinol in rats and dogs. NOAEL (no observed adverse effect level) for dogs was estimated to be more than 600 mg/kg/day; in rats the NOAEL was conservatively estimated to be 600mg/kg/day for males and 200 mg/kg/day for females.

- Montero R, Sánchez-Alcázar JA, Briones P, Hernández AR, Cordero MD, Trevisson E, Salviati L, Pineda M, García-Cazorla A, Navas P, Artuch R. Analysis of coenzyme Q10 in muscle and fibroblasts for the diagnosis of CoQ10 deficiency syndromes. Clin Biochem. 2008 Jun;41(9):697-700. Epub 2008 Mar 20.

- Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, Rasmussen C, Greenwood M, Leutholtz B, Willoughby D, Kreider R. Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. J Int Soc Sports Nutr. 2008 Mar 4;5:8.

One of the major findings of this study is that following acute ingestion of CoQ10, plasma CoQ10 levels were significantly correlated to muscle CoQ10 levels, maximal oxygen consumption and treadmill time to exhaustion. A trend for increased time to exhaustion was also observed following 2 weeks of CoQ10 supplementation (200 mg/day).

- Miles MV, Miles L, Tang PH, Horn PS, Steele PE, DeGrauw AJ, Wong BL, Bove KE. Systematic evaluation of muscle coenzyme Q10 content in children with mitochondrial respiratory chain enzyme deficiencies. Mitochondrion. 2008 Mar;8(2):170-80. Epub 2008 Feb 2.

- Baskaran R, Shanmugam S, Nagayya-Sriraman S, Kim JH, Jeong TC, Yong CS, Choi HG, Yoo BK. The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline. Arch Pharm Res. 2008 Jul;31(7):938-44. Epub 2008 Aug 14.

This pharmacokinetic study conducted in rats indicates an increased bioavailability of theophiline when given together with CoQ10 at high dosages. This finding suggests a close monitoring of theophiline in plasma levels when given with CoQ10.

- Mancini A, Leone E, Festa R, Grande G, Di Donna V, De Marinis L, Pontecorvi A, Tacchino RM, Littarru GP, Silvestrini A, Meucci E. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion. Metabolism. 2008 Oct;57(10):1384-9

Biliopancreatic diversion (BD) is a surgical procedure performed in patients with untreatable obesity, which also leads to altered lipid absorpation. Lowered plasma CoQ10 levels after BD highlight the importance of intestinal absorbance of CoQ10 and/or vitamin and cofactors necessary for its biosynthesis.

- Yang X, Yang Y, Li G, Wang J, Yang ES. Coenzyme Q10 attenuates beta-amyloid pathology in the aged transgenic mice with Alzheimer presenilin 1 mutation. J Mol Neurosci. 2008 Feb;34(2):165-71. Epub 2008 Jan 5.

Transgenic mice bearing the PS-1 mutation show selective increase of A42 (-amyloid), which is recognized to play an initial role in the pathogenesis of Alzheimer’s Disease. Treatment of the transgenic mice with CoQ10 significantly attenuated A42 overproduction in the cortex and decreased the levels of oxidative stress.

- Abdin AA, Hamouda HE. Mechanism of the neuroprotective role of coenzyme Q10 with or without L-dopa in rotenone-induced parkinsonism. Neuropharmacology. 2008 Sep 10. [Epub ahead of print]

In this experimental model of Parkinsonism CoQ10 administration showed a dose dependent amelioration of striatal complex I activity, ATP levels and Bcl-2 expression, together with a marked symptomatic improvement in catalepsy score.

- Murata T, Ohtsuka C, Terayama Y. Increased mitochondrial oxidative damage and oxidative DNA damage contributes to the neurodegenerative process in sporadic amyotrophic lateral sclerosis. Free Radic Res. 2008 Mar;42(3):221-5.

For the first time oxidized and reduced CoQ10 levels were analysed in the cerebral spinal fluid from patients affected by sporadic amyotrophic lateral sclerosis. The percentage of oxidized CoQ10 was correlated with the concentration of 8-OHdG suggesting that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of sporadic amyotrophic lateral sclerosis.

- Ausili A, Torrecillas A, Aranda F, de Godos A, Sánchez-Bautista S, Corbalán-García S, Gómez-Fernández JC.

Redox state of coenzyme Q10 determines its membrane localization. J Phys Chem B. 2008 Oct 9;112(40):12696-702.

- Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis.

Nat Clin Pract Neurol. 2008 Nov;4(11):600-9.

PMID: 18978800 [PubMed - in process]

This paper focuses on the recent rapid advances in PD (Parkins0n’s Didease) genetics revealing a prominent role for mitochondrial dysfunction in the pathogenesis of the disease. Within the novel therapeutic interventions that modify mitochondrial function a large phase III clinical trial in underway to examine whether high dose oral CoQ10 will slow disease progression.

- Abdel-Salam OM. Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42. PMID: 18991661 [PubMed - in process]

This review also considers novel and alternative neuroprotective therapies in Parkinson’s Disease, including CoQ10.

- Kubo H, Fujii K, Kawabe T, Matsumoto S, Kishida A, Hosoe K. Food content of ubiquinol-10 and ubiquinone-10 in the Japanese diet. J of Food Composition and Analysis. 2008: 21, 199-210.

This paper presents an extensive assessment of ubiquinol-10 and ubiquinone-10 content in Japanese foods. It confirms the relatively high CoQ10 levels in meat and fish and, on the basis of data on Japanese daily food consumption, it also calculates the estimated average daily intakes of CoQ10, which is slightly below 5 mg.

- Saito Y, Fukuhara A, Nishio K, Hayakawa M, Ogawa Y, Sakamoto H, Fujii K, Yoshida Y, Niki E. Characterization of cellular uptake and distribution of coenzyme Q(10) and vitamin E in PC12 cells. J Nutr Biochem. 2008 Jul 3. [Epub ahead of print]

This article successfully demonstrates that exogenous CoQ10, when added to a neuronal cell model culture, is uptaken and generates cellular concentrations up to 50 times higher than the endogenous CoQ content. Exogenous CoQ10 was mainly localized in the mitochondrial fraction, which is similar to the localization of the endogenous CoQ. Incubation with similar concentrations of alpha-tocopherol, resulted in a much lower uptake of alpha-tocopherol itself.