Clinical Uses of Coenzyme Q10 as a Supplement

Aimed at improving cellular bioenergetics, counteracting oxidative stress and slowing down some age-related pathologies

Cardiovascular disease & CoQ10

(1) Cardiac surgery – past clinical trials suggested improved postop cardiac function and reduced structural damage, recent RCT failed to demonstrate a difference in clinical outcomes

(2) CPR - CoQ10 with mild hypothermia after cardiac arrest/CPR – recent RCT demonstrated higher 3-month survival rate (68% vs 29%) and higher rate of good neurological outcome (36% vs 20%)

(3) CHF – recent RCT of patients with end-stage heart failure awaiting transplant, 60mg CoQ10 QD for 3 mos in addition to conventional therapy, showed improvement in dyspnea, NYHA class, nocturia, fatigue, and improved 6-min walk test (CoQ10 269 to 382m vs placebo 254 to 177m)

(5) HyperTG – in massive hyperTG resistant to treatment with fibrates and PUFA, CoQ10 leads to improved SBP, DBP, Cr, and lipoprotein (a) levels; larger decreases in TG when CoQ10 added to fenofibrate tx alone

Statins & CoQ10

Due to a common biosynthetic pathway of CoQ10 and cholesterol, statins adversely affect CoQ10 levels.

(1) Side effects of statins (myalgia, fatigue, rhabdo)

– may be from low CoQ10 (controversial)

- one study demonstrated worsening LV diastolic function in asymptomatic pts tx with atorvastatin that was reversed with CoQ10

- second study demonstrated decreased EF in hypercholesterolemic pts tx with simvastatin but did not find a correlation between amplitude of EF reduction and extent of reduction in plasma level of CoQ10

(2) Ischemic heart disease – combination of statins and CoQ10 (vs CoQ10 alone) had more effect on total chol/HDL ratio, plasma aggregability, and plasma NO concentration (no comparison of statins vs statins plus CoQ10) in patients with ischemic heart disease and revascularization

Mitochondrial myopathies & CoQ10

Different forms of mitochondrial myopathies respond to CoQ10 supplementation

- 2 case reports of response to CoQ10: pt c isolated mitochondrial myopathy without CNS involvement & pt c MELAS

- one study of 12 pts with proven defects of oxidative phosphylation treated with CoQ10, carnitine, vit B complex, vit C, vit K, lead to an increase in ATP synthesis by lymphocytes (from 34% reduction compared to controls to 12%) isolated to the effect by CoQ10, 3/12 patients demonstrated increase in energy levels and exercise tolerance

Parkinson’s disease & CoQ10

Data suggesting impairment of mitochondrial function and oxidative damage in brain of pt’s with PD. CoQ10 has been shown to be neuroprotective against ischemia due to mitochondrial toxins (malonte, 3-nitroproprionic acid, MMP).

- Phase II clinical trial – pts with early PD not on levodopa, treated with placebo or CoQ10 (1200 mg/day), showed an overall slowing of disability (measured by UPDRS) of 44% at 16 mos

Friedreich’s ataxia & CoQ10

Trial of 10 pts treated with CoQ10 and vit E, followed for 4 yrs – improvement in markers (including cardiac phosphocreatinine/ATP ratio, maximum rate of mitochondrial ATP synthesis, fractional shortening on echo, skeletal muscle phosphocreatinine/inorganic phosphate ratio), in addition to a slowing of progression of certain clinical features (measured by ICARS) compared to untreated pts

Migraine & CoQ10

RCT of 42 pts for migraine prophylaxis (CoQ10 100mg TID) – demonstrated reduction in attack frequency (14.4% response to placebo vs 47.6% to CoQ10, NNT 3), headache days, and days with nausea in the 3rd treatment month

Macular degeneration & CoQ10

RCT of 101 pts treated with acetyl-L-carnitine, n-3 fatty acids, and CoQ10 – demonstrated improvement in visual field mean defect (2% of treated pts had clin sig dec in VFMD vs 17% of placebo), visual acuity, foveal sensitivity, and drusen-covered area of fundus

Asthenozoospermia & CoQ10

Decreased levels of CoQ10 in seminal plasma and sperm of infertile men with asthenozoospermia

- uncontrolled study of 22 pts with idiopathic asthenozoospermia (<50%>

References

1. Littarru GP & Tiano L. “Clinical aspects of coenzyme Q10: an update.” Current Opinion in Clinical Nutrition and Metabolic Care 8:641-646, 2005.

2. Rosenfeldt F, Marasco S, Lyon W et al. “Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of mitochondrial tissue.” J Thorac Cardiovasc Surg 129:25-32, 2005.

3. Damian MS, Ellenberg D, Gildemeister R, et al. “Coenzyme Q10 combined with mild hypothermia after cardiac arrest.” Circulation 110:3011-3016, 2004.

4. Berman M, Erman A, Ben-Gal T, et al. “Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomised, placebo-controlled study.” Clin Cardiol 27:295-299, 2004.

5. Cicero AF, Derosa G, Miconi A, et al. “Treatment of massive hypertriglyceridemia resistant to PUFA and fibrates: a possible role for the coenzyme Q10?” BioFactors 23:7-14, 2005.

6. Silver MA, Langsjoen PH, Szabo S, et al. “Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction.” Am J Cardiol 94:1306-1310, 2004.

7. Colquhoun DM, Jackson R, Walters M, et al. “Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans.” Eur J Clin Invest 35:251-258, 2005.

8. Chapidze G, Kapanadze S, Dolidze N, et al. “Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins.” Georgian Med News 1:20-25, 2005.

9. Lalani SR, Vladutiu GD, Plunkett K, et al. “Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency.” Arch Neurol 62:317-320, 2005.

10. Berbel-Garcia A, Barvera-Farre JR, Etessam JP, et al. “Coenzyme Q10 improves lacitc acidosis, strokelike episodes, and epilepsy in a patient with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes).” Clin Neuropharmacol 27:187-191, 2004.

11. Bresolin N, Doriguzzi C, Ponzetto C, et al. “Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial.” J Neurol Sci 100:70-78, 1990.

12. Beal MF. “Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q10 as a potential treatment.” J Bioenerg Biomembr 36:381-386, 2004.

13. Shults CW, Oakes D, Kieburtz K, et al. “Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.” Arch Neurol 59:1541-1550, 2002.

14. Hart PE, Lodi R, Rajagopalan B, et al. “Antioxidant treatment of patients with Friedreich’s ataxia: a four-year follow-up.” Arch Neurol 62:621-626, 2005.

15. Sandor PS, Clemente L, Coppola G, et al. “Efficacy of coenzyme Q10 in migraine prophylaxis: a randomised controlled trial.” Neurology 64:713-715, 2005.

16. Feher J, Kovacs B, Kovacs I, et al. “Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of actyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.” Ophthalmologica 219:154-166, 2005.

17. Balercia G, Mosca F, Mantero F, et al. “Coenzyme Q10 supplementation in infertile men with idiopathic astehnozoospermia: an open uncontrolled pilot study.” Fertil Steril 81:93-98, 2004.

Category: Pharmacology Notes