Coenzyme Q10

Coenzyme Q10 (CoQ 10), also known as ubiquinone is often described as a vitamin or at least a vitamin-like substance. However it is not strictly a vitamin as it can be synthesised in the liver. CoQ 10 is synthesised from the amino acid tyrosine (this synthesis in turn requires other vitamins and minerals) but is also absorbed from a wide variety of foods.
A lot of research as been done yielding interesting results. It is useful to try and evaluate these to identify indications for supplementation in health and disease. As with other vitamins and dietary supplements the strongest case for use can be made in conditions where deficiency is associated with disease and where supplementation corrects or prevents the disease. It is more difficult to establish benefit in health maintenance and disease prevention. In common with other naturally occurring antioxidant compounds many claims are made for benefit through antioxidant activity.

In common with other coenzymes it is a cofactor upon which other enzymes depend for their function. It appears to be a coenzyme for a number of cell enzymes including enzymes within the mitochondrial oxidative phosphorylation pathway which produces adenosine triphosphate (ATP). This is fundamental to energy production within cells. It may also have a roll as an antioxidant and it undoubtedly has antioxidant activity.^1,2,3 It was discovered in the United States and England in 1957 and by the 1970s could be produced in large enough quantities to allow more research to be done.

Since the 1980s it has been possible to measure normal blood and tissue levels of CoQ 10. It has thus been possible to define deficiency of CoQ 10 and possible associated disease. Deficiency can arise through:

• Reduced biosynthesis
• Increased utilisation
• Reduced dietary intake
• A combination of these factors (probably most often the cause)

Some examples of possible indications and interesting research findings include:

• Corticosteroids in asthma reduce CoQ 10 levels and supplementation with CoQ 10 reduces the dosage of corticosteroids required to control asthma and hence the potential for steroid side effects⁴
• CoQ 10 levels are low in hyperthyroidism and high in hypothyroidism⁵
• In male infertility low CoQ 10 levels have been found in seminal fluid and supplementation improved sperm motility^6,7,8
• CoQ 10 levels in cord blood were lower in normal woman compared to women with preeclampsia⁹
• Primary CoQ 10 deficiency does exist but is very rare. It causes an encephalomyopathic disease and supplementation has been reported to benefit the myopathy.^10,11,12 This is not replicated in other studies.¹³
• Hormone replacement therapy (HRT) lowers serum CoQ 10 levels and it is postulated that this may increase cardiovascular disease risk.¹⁴
• Administration of HMG-CoA reductase inhibitors ('statins') has been associated with a reduction in CoQ 10 levels (due to inhibition of mevalonate synthesis).^15,16 The myopathy associated with statins is poorly understood.^17,18 There has been speculation that this reduction in CoQ 10 may be associated with statin induced myopathy.¹⁹ However the reduction may just reflect reduction in the lipoprotein carriers of CoQ 10 and may not be statin specific.²⁰ The reduction of CoQ 10 is corrected by supplementation and does not affect the cholesterol lowering effect of simvastatin.²¹ There are studies to support supplementation with CoQ 10 in patients on statins.^22,23,24 However supplementation if used should not divert from routine monitoring and use of lowest effective dose of statin.^25,26 A recent review of the literature did not recommend routine CoQ 10 supplementation but suggested that certain subpopulations might benefit (patients with familial hypercholesterolaemia, patients with heart failure, patients over 65 years).²⁷ Other reviews highlight the lack of evidence to support routine CoQ 10 supplementation even though there are few safety concerns with such supplementation.²⁸ More research is needed to support such a recommendation. One of the limitations with some studies is that they measure plasma CoQ 10 rather than tissue levels.²⁹ There are lots of studies indicating that the clinical benefits of statins outweigh the low rates of adverse effects.³⁰
• There are good theoretical reasons for expecting benefit from CoQ 10 supplementation in heart disease.²⁹ There is concern that therapies (such as statins) that may lower CoQ 10 levels may also precipitate worsening of heart failure particularly in those patients who already have low CoQ 10 levels associated with heart failure. A lot of clinical studies on congestive cardiac failure and CoQ 10 supplementation have been done and some report clinical improvements. However concerns about the designs of these studies (including the small numbers of patients and the use of plasma CoQ 10 measurement) have limited acceptance of the findings.³¹ There have also been trials on use in idiopathic dilated cardiomyopathy but not showing statistically significant improvement.³²
• Prevention of vascular disease and cancer with antioxidants is a theoretical possibility. It has been suggested that antioxidants are best taken in combination.³³ It has been suggested that wide-spread use of antioxidants for protective effects should await the results of ongoing clinical trials.^34,35 Some trial results are not encouraging so far failing to confirm protective effect from other antioxidant vitamins.³⁶ Some express high hopes for CoQ 10 in neurodegenerative disease, cancer, cardiovascular disease and diseases of aging.³⁷
• There may be a neuroprotective effect from the toxic effects of cocaine and methamphetamine according to animal research on mice.³⁸
• Lower levels of CoQ 10 have been found in the follicular phase of the menstrual cycle compared with the luteal phase. Oral contraceptive use significantly reduced CoQ 10 levels but the clinical significance of this is unclear and more research is needed.³⁹
• Changes in levels of CoQ 10 in the cerebrospinal fluid of patients with Parkinson's disease have been found, but the clinical significance is unclear.⁴⁰
• There are some interesting reports suggesting possible therapeutic benefit of CoQ 10 in Huntingdon's disease (HD). The suggestion is that the mitochondrial dysfunction found in HD may be improved with CoQ 10 supplements.⁴¹
• It has also been tried with apparent benefit in Friedreich's Ataxia.⁴²
• It is recommended in migraine prophylaxis.

It appears to be safe and the reduced form (ubiquinol) when fed to healthy volunteers at different doses over 4 weeks did not cause safety concerns or adverse events.⁴³ Other safety assessments have been favourable.⁴⁴ It seems sensible to avoid supplementation in pregnancy.

The possible indications for CoQ 10 are many and varied. However with current evidence it is difficult to make firm recommendations. Some patients may initiate therapy themselves as it is widely available.
CoQ 10 dissolved in an oil matrix rather than a crystalline form appears to be better absorbed.¹ Dosages used in clinical trials have varied, but there appears to be a trend towards higher doses. Recommendations on dosage often relate to specific diseases and there is no firm recommendation for use in prevention of disease. What dosage should be taken remains an open question with suggestions in disease states ranging from 30mg per day to 300mg per day.

It is important that monitoring of any disease or condition be continued. No CoQ 10 specific monitoring is recommended in routine clinical use. CoQ 10 levels can be measured but such testing should certainly be discussed with the laboratory.

A possible interaction with coumarin anticoagulants has been reported at high doses.

CoQ 10 was first isolated in 1957 by a Dr Crane in Wisconsin and by Professor Morton in England. Professor Morton came up with the name ubiquinone (ubiquitous quinone). Production of large quantities was perfected in the 1970s in Japan enabling larger scale clinical trials. The role of CoQ 10 in the energy production within mitochondria was better understood after the contribution of 1978 Nobel Prize winning scientist Peter Mitchell.