Co-enzyme Q10

Scientific/common names

Coenzyme Q10 is also known as: CoQ10, Q10, vitamin Q10, Ubiquinone, Ubidecarenone, Mitoquinone, Adelir, Heartcin, Neuquinone, Taidecanone and 2, 3 dimethoxy-5 methyl-6-decaorenyl benzoquinone.

Ingredients

Coenzyme Q10 is produced naturally by the body. In terms of dietary intake, CoQ10 is found in meat, fatty fish (for instance, sardines and mackerel), whole-grain cereals, brown rice, pasta, wholemeal bread, soya products, nuts and also vegetables (especially broccoli and spinach). Commercially, CoQ10 is made by fermenting beets and sugar cane with yeast.

Application and dosage

CoQ10 is sold as a dietary supplement and is usually administered by mouth as a pill (capsule or tablet), however, CoQ10 can also be given intravenously. According to proponents, manufacturers and providers, doses range from 50mg a day for maintenance to 400mg a day for “therapeutic” effects. The observed safety level (OSL) is 1200mg/day/person 54.

Claims of efficacy / mechanisms of action / alleged indication

A “coenzyme” is a molecule that is necessary for the proper functioning of an enzyme. The “Q” refers to the quinone chemical group and “10” is a particular type of quinone. In the human body, CoQ10 is part of the chain reaction necessary for energy production in cells. As well as this, some researchers class CoQ10 as an antioxidant 2 as it is believed to protect against excess free radicals which are thought to be implicated in tumour development. CoQ10 is also claimed to be an immunostimulant, however, this is based on not more than one study showing increases of IgG levels 3. CoQ10 is found in most tissues; however the liver, heart, kidneys and pancreas hold the highest concentrations and the lungs the lowest 4. Levels of CoQ10 are found to decrease with age. This is due to a decrease in mitochondrial CoQ10 content 5. Investigations also suggest lower tissue levels in people with heart disease 6 and cancer 1,9. Due to this finding, researchers have started to investigate whether CoQ10 could be useful in treating diseases such as cancer.

A study concluded that CoQ10 concentrations were significantly lower in melanoma patients than in a control group. Patients in whom metastases developed in this study had lower levels of CoQ10 than those who did not develop metastases 1,47. Observational studies have reported reduced levels of CoQ10 in diseased breast tissue, but it is not clear if this is simply part of the bodies natural response to cancer 50.

A 2010 cohort study concluded that higher CoQ10 levels in post-menopausal women may be associated with an increased risk of breast cancer 55. A further prospective study reported an inverse relationship between circulating CoQ10 levels and breast cancer risk. The authors propose that a possible explanation of the opposing results is that women at either extreme of CoQ10 levels may be at an increased risk for breast cancer. Both studies are consistent in that women with circulating CoQ10 levels in the range of 500-800 ng/mL have the lowest risk if developing breast cancer 56. The results of a multi-ethnic cohort study suggest that moderate levels of circulating CoQ10 may be optimal for the reduction of prostate cancer risk, but the findings were not statistically significant 57.

At present it is unclear how and whether levels of CoQ10 alter when people are ill, therefore it is unknown if supplementation is necessary at all. Clinical and pre-clinical studies suggest that it helps protect the heart from toxic damage caused by the chemotherapy anthracycline. Although there has been concern that CoQ10 may interfere with the anticancer effects of anthracyclines, as it protects the heart from toxic damage, it is thought that higher doses of anthracycline may be able to be given which could enhance the anticancer effect of the chemotherapy 51.

According to proponents of CoQ10, there are three main potential benefits for taking it as a supplement: a) it may be an anti-cancer agent, b) it may support the body, lessening the toxic effects of chemotherapy and c) it may alleviate chronic fatigue.

Prevalence

In terms of prevalence of the use of the use of CoQ10, it is widely used in Japan, with government approval in relation to cardiovascular disease treatment 7. CoQ10 is also used in Europe 8 and North America 7, with the majority of CoQ10 products being provided by Japanese manufacturers 7.

Legal issues

Coenzyme Q10 is classed as a nutraceutical and therefore suppliers can only advertise in terms of health improving properties instead of medical claims 7.

Cost(s) and expenditure

A good quality CoQ10 supplement can cost between 20 and 70 Euros for 60 capsules. Since there are no clear guidelines on dosage and length of treatment, it is not possible to give an overall cost.

Does CoQ10 work as an anti-cancer agent?

Controlled clinical studies

Italian researchers who conducted a three year (non-randomised) study with a sample of melanoma patients (n=81) found that the group treated with CoQ10 alongside interferon reported improved quality of life (favourable mood effects, reduction in physical weakness and in the severity of tinnitus) compared to the control group who received interferon only. The patients with stage II melanoma in this group also appeared to have a lower rate of recurrence. Further trials with more patients are being undertaken by this research team 46.The same researchers concluded that plasma CoQ10 levels are a powerful and independent prognostic factor and can be used to estimate the risk for melanoma progression 47. A trial by a team of Indian researchers using CoQ10 in a group of women (n=210) undergoing tamoxifen treatment reported reduced levels of angiogenesis markers 39.

Uncontrolled clinical studies

One uncontrolled study in Denmark followed the progress of 32 people with breast cancer for 18 months who were given antioxidant supplements including CoQ10 after or concomitantly with conventional anticancer treatment 12. At the end of this period, six people were in remission and all of the 32 were alive and reporting improved quality of life, less painkiller use and less weight loss. In a follow-up study, all 32 people were alive at 24 months 13.

Case reports

In a different study conducted by the same researchers, three people with breast cancer and taking high doses of CoQ10 were investigated for three to five years 14. All three experienced remission.

A case history review documented anecdotal reports of CoQ10 suggesting a positive survival effect on people with different cancers 11.

Overall there is no evidence to support CoQ10 working as an anti-cancer agent. The above controlled trials 39,46-47 were not high-quality randomised clinical trials and in the uncontrolled clinical studies and case reports 12-14 control groups were not used, patients were also taking supplements other than CoQ10, and effective anticancer treatments were also given.

Clinical trials of analogues of CoQ10 and CoQ10 combination products

Trials in which CoQ10 is used as part of a supplement combination appears to show some anti-cancer benefit 36-38 and improved blood chemistry profile 40-42, although an earlier trial did not show benefit 35.

Pre-clinical studies

There is some preliminary evidence from laboratory and animal studies that chemicals very similar to CoQ10 (analogues of CoQ10) 9-10 and CoQ10 used as part of an antioxidant combination 43-45 have anti-cancer effects.

Does CoQ10 work as a protector against adverse effects of chemotherapeutic agents?

Reviews

A Cochrane systematic review reported that no definite conclusions can be made about the efficacy of different cardioprotective agents for cancer patients receiving anthracyclines 48. It only included one study on CoQ10, however, that is reported below by Iarussi et al. 23.

A 2008 review by Nicolson and Conklin stated that, although limited in number, clinical studies support pre-clinical data that suggests CoQ10 protects the heart from the cardiotoxicity of anthracyclines. They noted that the impact of CoQ10 on the anti-neoplastic efficacy of anthracycline-based chemotherapy has not yet been studied 49.

A review by Roffe et al. 18 states that there is some evidence of a protective benefit from CoQ10, however, the authors conclude that the studies reviewed are all methodologically flawed and the results not conclusive. The article reviewed several pre-clinical and clinical studies, although the numbers of people included in the clinical studies were small (maximum n=80), so the results need to be interpreted with caution. The review stated that many unanswered questions remain about the use of CoQ10 alongside anthracycline. Little is known about how long these effects can last for or the best way to administer CoQ10 (what levels should be taken/should it be administered with food etc). Most importantly, little is still known about how it may affect the anti-tumour activity of anthracycline 51.

Bryant et al. conducted a systematic review to evaluate technologies to reduce anthracycline-induced cardiotoxicity in children. The review presented the results of one study that reported a protective effective of CoQ10 on cardiac function 52.

Controlled clinical trials

Several trials have looked at whether CoQ10 protects against chemotherapy induced cardiotoxicity.

Takimoto et al. 19 conducted a small randomised clinical trial (n = 40) on lung, breast and thyroid patients treated with doxorubicin chemotherapy. The experimental group was given CoQ10 and the patients were found to have improved heart capacity compared to the control group. However, no significant difference in arrhythmia frequency or other indicators of heartbeat malfunction were seen.

Akihama et al. 20 also conducted a small (n = 19) placebo-controlled, double-blind study with leukaemia and lymphoma patients taking anthracycline and also CoQ10 in the experimental group. No significant difference between control and experimental groups was found.

In another randomised clinical trial, Okuma et al. 21 studied a relatively large group of participants (n = 80) with a range of different cancers. They found CoQ10 had a significant stabilising effect on the heart.

In 1986, Lucarelli et al. 22 found CoQ10 to have a beneficial effect against anthracycline cardiotoxicity in a controlled clinical trial with 30 haematological cancer patients. This small study did, however, not report any statistics for any significant effects.

Iarussi et al. 23 conducted a small randomised clinical trial (n = 20) to look at the protective effect of CoQ10 in leukaemia and lymphoma patients’ heart function. They found less heart damage for the CoQ10 group, but crucially did not report any statistics for this, thereby not demonstrating whether CoQ10 had a therapeutic effect This study has further methodological limitations; both the participants and the providers were not blinded to the treatment 48.

Pre-clinical data

Animal evidence supporting the cardioprotective effects of CoQ10 has been seen on the heart muscles of mice, rats and rabbits given chemotherapy (Adriamycin) 15 and Doxorubicin 58. However, the same positive benefit was not found in another study with Adriamycin 16 and also radiotherapy 17. A further mice study concluded that CoQ10 ameliorated acute cystoplatin nephrotoxicity 59.

It therefore appears that although there is some evidence that CoQ10 works as a protector against adverse effects of several chemotherapeutic drugs, further higher quality trials are still needed to confirm this.

Two reviews conclude that data from preclinical and clinical studies show that CoQ10 is highly safe as a dietary supplement 53-54. The observed safety level (OSL) is 1200mg/day/person 54. Higher CoQ10 levels in post-menopausal women may be associated with increased breast cancer risk 55 and CoQ10 has been shown to promote the survival of tumour cells treated with anti-cancer drugs in some in vitro studies 25.

Adverse effects

Documented adverse effects include nausea, upper abdominal pain, rashes, dizziness, sensitivity to light, irritability, fatigue, headache, heartburn 26-27. In doses over 100mg, if taken in the evening, Coenzyme Q10 may cause mild insomnia 28 as it may raise energy levels six to eight hours after being taken.

Contraindications

Coenzyme Q10 is contraindicated for pregnant or lactating women 29, those with diabetes and high blood pressure 4. Also, excessive exercise should be avoided whilst taking Coenzyme Q10 29.

Drug interactions

Theoretically, as CoQ10 has antioxidant properties, and as several chemotherapeutic agents and radiotherapy work using “oxidative stress” (the opposite of antioxidant action), taking CoQ10 may limit the effectiveness of these therapies 7,32.

CoQ10 may increase the risk of blood clotting or bleeding, and therefore may possibly interfere with warfarin 32. However, according Engelsen 33, CoQ10 does not influence the clinical effect of warfarin. Natural levels of CoQ10 may possibly be depleted when taking drugs that lower cholesterol (statins) or blood sugar levels 7,24,34 and also beta blockers 7,28.

Quality issues

Quality and composition of CoQ10 products may differ between manufacturers 30-31.