Advice

Key Points

Key Points

The content of this evidence summary was up-to-date in March 2017. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Regulatory status: Co-enzyme Q10 has no licensed indications as a medicine in the UK.

Overview

This evidence summary discusses 3 case reports in a total of 6 children with mitochondrial disorders. Because this evidence is very limited, this evidence summary also discusses the best available evidence on the use of co-enzyme Q10 in adults and young people with mitochondrial disorders.

The symptoms of the children described in the case reports were diverse and included motor/muscle symptoms, neurological symptoms, nephrotic syndrome and hypoparathyroidism. Symptoms of all 6 children were reported to improve with co-enzyme Q10 treatment. However, as uncontrolled observational studies in individual patients, these case reports are prone to bias and other methodological problems. They also provided very limited data on objective measurable outcomes. In addition, mitochondrial disorders are a heterogeneous group of rare diseases and the children included in these case reports may not represent all types of patients seen in clinical practice.

The best available evidence on the use of co-enzyme Q10 in adults and young people with mitochondrial disorders consists of 2 randomised controlled trials (RCTs) and 1 non-randomised study. These studies showed no statistically significant benefit for co-enzyme Q10 compared with placebo for the majority of outcomes assessed including mitochondrial disease-specific activities of daily living and quality of life assessment scores, handgrip fatigue tests and sustained endurance strength. However, the studies had a number of important methodological limitations, were of short duration and included only small numbers of participants. They may therefore have been insufficiently powered to detect any true differences between placebo and co-enzyme Q10. In the non-randomised study, after 6 months treatment with co-enzyme Q10 there was a statistically significant increase in the global Medical Research Council (MRC) muscle scale score and a statistically significant decrease in post-exercise serum lactate levels from baseline. However, the clinical significance of these changes is unclear.

There is currently no established treatment for mitochondrial disorders and the clinical management is largely supportive. The studies included in this evidence summary provide insufficient evidence to evaluate the place in therapy of co-enzyme Q10 for the treatment of mitochondrial disorders in children. The case reports and the studies in adults and young people used a wide variety of doses and formulations of co-enzyme Q10.

A summary to inform local decision-making is shown in table 1.

Table 1 Summary of the evidence on effectiveness, safety, patient factors and resource implications

Effectiveness

  • No statistically significant difference between co-enzyme Q10 at a dose of 600 mg twice daily and placebo for mitochondrial disease-specific activities of daily living and quality of life assessment scores or mean maximal isometric forearm strength (Glover et al. 2010, RCT in adults; n=30, crossover study 60 days taking both co-enzyme Q10 and placebo).

  • No statistically significant difference between co-enzyme Q10 at a dose of 160 mg daily and placebo for fatigability in activities of daily living score or sustained endurance strength (mean time taken in seconds to perform specified activities) [Chen et al. 1997, crossover RCT in adults and young people, n=8, 3 months taking co-enzyme Q10 and 1 month taking placebo].

  • Statistically significant increase in the global MRC muscle scale score with co-enzyme Q10 at a dose of 160 mg daily compared with placebo. However, the clinical significance of this increase (from approximately 83% to 87%) is unclear (Chen et al. 1997).

  • Statistically significant increase in the global MRC muscle scale score from baseline after 6 months treatment with co-enzyme Q10 at a dose of 2 mg per kg daily (from approximately 89% to 91%) and statistically significant decrease in post-exercise serum lactate levels (from approximately 68 to 52 mg %). The clinical significance of these changes is unclear (Bresolin et al. 1990, study in adults and young people, n=44).

  • Case reports in 6 children suggest beneficial effects but the clinical significance of this evidence is hard to assess.

Safety

  • Co-enzyme Q10 may reduce insulin requirements in people with diabetes and may enhance or reduce the anticoagulant effect of warfarin (BNFc).

  • The European Public Assessment Report (EPAR) for idebenone (EPAR: Raxone) includes blood count abnormalities, abnormal liver function and hepatitis as potential safety concerns (based on studies in Leber's Hereditary Optic Neuropathy and other diseases).

  • The studies included in this evidence summary provide no information on the safety of co-enzyme Q10.

Patient factors

  • Possible side-effects of co-enzyme Q10 include nausea, diarrhoea, heartburn and rarely headache, irritability, agitation and dizziness (BNFc).

  • The studies included in this evidence summary provide no information on the tolerability of co-enzyme Q10.

Resource implications

  • Co-enzyme Q10 formulations for prescription are available from 'special-order' manufacturers or specialist importing companies. Costs will vary depending on the brand or manufacturer.

  • Idebenone is a synthetic analogue of co-enzyme Q10. It is licensed for the treatment of visual impairment in adolescent and adult patients with Leber's Hereditary Optic Neuropathy (SPC: Raxone). It costs £6364.00 for 30 days' treatment (MIMs, March 2017).