Coenzyme Q10

This summary is currently being updated. The version published here was last updated in June 2016.

  • Coenzyme Q10 (CoQ10) is an organic compound produced by the body in small quantities.
  • Evidence to support CoQ10 working as an anti-cancer agent is insufficient.
  • Evidence to support a proposed theory that CoQ10 may counteract cancer-related fatigue is lacking.
  • Weak evidence is available that CoQ10 protects the heart from chemotherapy-induced toxicity.
  • Only minor side effects have been reported.

Coenzyme Q10 (CoQ10) is an organic compound which is synthesized endogenously by the human body and plays a critical part in the electron transport of the mitochondrial respiratory chain. It also has extracellular oxidative and antioxidant effects.

The need to supplement CoQ10 via the diet is very low. Nevertheless, CoQ10 supplements are widely sold and advertised with many health-related claims.

The reason for this is that there have been reports about the preventive effects of CoQ10 supplements on cancer. The underlying mechanisms of action are thought to be immunomodulatory and antioxidant in nature.

There is limited evidence that CoQ10 is effective in cancer prevention or can protect against the adverse effects and toxicity of cancer treatments. A prospective study indicated some evidence of a decrease in the recurrence rate of malignant melanoma; five randomised controlled trials showed cardioprotective effects in anthracycline-based chemotherapy; one study demonstrated a decrease in fatigue among breast cancer patients; and another prospective study suggested a reduction in the adverse effects of treatment with interferon. These findings need to be interpreted with great caution, however, since the clinical trials had numerous methodological flaws.

Adverse effects of CoQ10 rarely occur, are dose-dependent, and usually not severe. Due to its structural similarity with Vitamin K, an interaction with coumarin derivatives is possible, although it has only been described in individual cases. 

Citation

Rottorf M, Cooke H, CAM Cancer Consortium. Coenzyme Q10 [online document], Jun 21, 2016.

Document history

Latest update: June 2016

Next update due: June 2019

Description

CoQ10 is a naturally produced molecule found in the membranes of nearly all of the body’s cells. Particularly high concentrations are located in the inner mitochondrial membrane, although it is also found in the membranes of peroxisomes and lysosomes1

Scientific/common names

CoQ10 is structurally related to Vitamins K and E. The molecule structure is 1,4-benzoquinone, which has a characteristic isoprenoid tail.  The structure is what gives CoQ10 its name: the “Q” refers to the molecule’s quinone structure and the “10“ to the lipophilic isoprenoid chain of 10 subunits2. The name “ubiquinone” is often used to describe CoQ10; the term is taken from the ubiquity of the substance in a number of natural foods and in the human body as well as its quinone structure3. CoQ10 is also known as Vitamin Q10, ubidecarenon, mitoquinone, adelir, heartcin, neuquinone, and taidecanone.

Ingredients

CoQ10 naturally occurs in meat, fatty fish (such as sardines and mackerel), eggs, whole-grain cereals, rice, soya products, nuts, and vegetables (especially broccoli and spinach)1.

Application and dosage

The mean amount of CoQ10 obtained from the diet is a mere 3-10mg/d, and the body meets any additional need for CoQ10 by means of endogenous synthesis from precursors of cholesterol biosynthesis. As a result, in healthy individuals there is generally no CoQ10 deficiency4-5,44-45. The reference range of the CoQ10 concentration in serum/whole blood lies between 600-1000µg/l6.

CoQ10 is sold as a dietary supplement and usually taken orally as a capsule or tablet. It can also be administered intravenously. Due to its lipophilic nature, CoQ10 is absorbed more effectively when taken with high-fat foods. Consequently, intravenous CoQ10 is available as lipid preparations2. Dosages of 50-3000 mg/day are used in clinical studies.

History

CoQ10 was first isolated in 1957 and then described as a benzoquinone structure one year later7,8. Commercially produced CoQ10 is made by microbial fermentation processes9.

Several studies conducted since the 1960s have determined lower serum concentrations of CoQ10 in a variety of cancers (including breast, lung, prostate and colon). This led to increasing interest in CoQ10 as a potential agent in cancer prevention2. Furthermore, there have been anecdotal reports of CoQ10 playing a part in the remission of breast cancer and regression of metastases10-11.

Claims of efficacy / mechanisms of action / alleged indication

Dietary supplementation of CoQ10 is said to prevent the development or progression of cancer. The data from epidemiological studies, however, are not consistent. They show an inverse relationship between serum CoQ10 levels and the risk of disease / progression of breast cancer, multiple myelomas and malignant melanoma7,12,13. At the same time, they also indicate that higher CoQ10 levels in post-menopausal women may be associated with a greater risk of breast cancer14. A possible explanation for the latter may be that high concentrations of CoQ10 can have pro-oxidative effects on tissue15. CoQ10 is said to lower the cardiotoxic effects of certain chemotherapy drugs and mitigate the extent of chronic fatigue syndrome.

As a carrier molecule, CoQ10 has a critical function in the mitochondrial respiratory chain and the related production of oxidative energy. In addition, CoQ10’s antioxidant and immunomodulatory mechanisms of action have been hypothesized on the basis of experimental and epidemiological data:

  • In one clinical study, lower serum cytokine levels were reported in breast cancer patients who received CoQ10 supplements16.
  • Older studies show that in comparison with placebo, CoQ10 produces greater increases in antibody titres of healthy volunteers who were recently vaccinated against HBV17,18. A trial among healthy volunteers showed that CoQ10 can cause a significant increase in the CD4/CD8 cell ratio19.
  • CoQ10 is a major endogenous antioxidant20 which counteracts the oxidation of proteins, lipids and DNA3. Its protective effects against free radicals may involve stabilizing the cell membrane2.
  • One trial in breast cancer patients indicated evidence of lower concentrations of matrix metalloproteases in those who took CoQ1016.
  • In one animal study on hepatocellular cancer, CoQ10 stabilised the concentration of antioxidative enzymes and lowered the TNF-alpha levels as well as reducing the activity of NO synthase and cyclooxygenase-2.
  • Data from animal studies suggest that CoQ10 can protect against anthracycline-induced cardiotoxicity and nephrotoxicity15,21-23 as well as cisplatin-induced nephrotoxicity24 and neurotoxicity1.
  • Preclinical data from a study of healthy volunteers shows evidence that CoQ10 has positive effects on physical performance and subjective symptoms of fatigue both during and after physical exertion32. It is postulated that the molecular mechanism of action here is caused by CoQ10 supplementation compensating for mitochondrial dysfunction, which can take place in severe chronic diseases and may be a contributing factor to chronic fatigue syndrome25,26.

Prevalence

According to an EU-wide survey of nearly 300 breast cancer patients, some 4-5% of this cohort took CoQ10 as a complementary treatment27

Legal issues

CoQ10 is classified as a nutraceutical and may be sold as such. Suppliers may therefore only advertise in terms of its health-improving benefits and are not allowed to make claims of medical efficacy28. Since the 1970s, CoQ10 has been marketed in Japan for treating cardiovascular disease29.

Costs and expenditure

CoQ10 costs between €10 - 35 for 60 capsules (with doses ranging from 10 - 100 mg per capsule).

Adjuvant therapy

Controlled clinical studies

A two-arm, non-randomised trial compared the effects of CoQ10 (400mg/d, oral) on the recurrence rate in melanoma patients (n=81) who received three years of adjuvant therapy with recombinant IFNα-2b and CoQ10 versus no adjuvant therapy30. In the CoQ10 treatment group, the recurrence rate was significantly lower after 5 years of follow-up. The quality of the data was not good, however, and there is a great risk of bias due to the lack of randomisation and the small patient sample.

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

Reviews

A systematic review analysed the issue of whether oral administration of CoQ10 improved the tolerability of chemotherapy and reduced adverse events and toxicity31. The review examined five controlled interventional studies in which patients with different malignant haematological systemic diseases or solid tumours were given CoQ10 at doses of 90-240mg/d concomitantly with anthracycline chemotherapy. Three of the five studies reported positive effects on surrogate parameters of cardiac function. The authors of the review regarded this as potential evidence of CoQ10 reducing the cardiotoxicity of anthracycline chemotherapeutic agents. However, they also determined the risk of bias in the studies to be very high, thus greatly limiting the strength of the findings.

Controlled clinical trials

A two-arm, randomised, double-blind, placebo-controlled study examined the effect of CoQ10 on chronic fatigue and health-related quality of life in 236 breast cancer patients4. The intervention group received oral CoQ10 (300mg/d) for 24 weeks. There was no difference between the CoQ10 and placebo groups with regard to fatigue and quality of life. The risk of bias here is seen as low.

The aforementioned two-arm non-randomised trial in melanoma patients had as secondary endpoints the effects of CoQ10 on adverse effects of interferon (IFNα-2b)30. The subjective rating by the treatment group (IFNα-2b + CoQ10) stated that there was a significant difference in the rate of adverse effects (such as fatigue or weakness), which occurred not at all or only in a mild form in comparison with the non-treatment group. Since the study was not blinded, there is a high risk of bias in these findings.

Two reviews of preclinical and clinical data concluded that CoQ10 is very safe as a dietary supplement33,34. The observed safety level (OSL) is 1200 mg/day, and oral administration for up to 30 months is regarded as safe33. In children, a daily dose of max. 10mg/kg body weight is considered safe; in pregnant women, a maximum of 200mg/day35

Adverse effects

The dose-dependent adverse effects that have been documented are nausea, acid reflux, upper abdominal pain, allergic dermal reactions, sensitivity to light, dizziness, irritability, headache, fatigue, and, if taken in the evening, mild insomnia. The prevalence of adverse events is reported at < 1% of users8,37,38. Doses over 100mg/d should be redistributed to 2-3 doses per day38. A monograph issued by the Natural Medicines Comprehensive Database (NMCD) reports several different clinical studies in which no severe adverse events occurred35

Contraindications

There are no mentions of any contraindications for CoQ10 supplements in international literature35

Drug interactions

Theoretically, CoQ10’s antioxidant mechanism of action could mean that it may impact the efficacy of some chemotherapeutic agents (such as anthracycline and cyclophosphamide) as well as radiotherapy. Recent in-vitro studies, however, have shown that CoQ10 does not affect the antineoplastic properties of doxorubicin39.

There are individual case reports which suggest that CoQ10 can reduce the efficacy of coumarins40-42, a phenomenon that can be explained by the structural similarity between CoQ10 and Vitamin K2. A small-scale randomised trial showed no change in the INR levels of patients who received coumarins and CoQ10 in doses of up to 100mg/d for four weeks43.

Taking CoQ10 can lower the need for insulin in patients with diabetes8,44 and the Natural Medicines Comprehensive Database describes CoQ10’s potential hypotensive effects which should be taken into account in antihypertensive treatment35.

Quality issues

The quality and composition of CoQ10 products may differ between manufacturers45,46.

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  18. Barbieri B, Lund B, Lundstrom B, Scaglione F: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study. Biofactors 1999; 9(2-4):351-357.
  19. Folkers K, Hanioka T, Xia LJ, McRee JT, Jr., Langsjoen P: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem Biophys Res Commun 1991; 176(2):786-791.
  20. Frei B, Kim MC, Ames BN: Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci U S A 1990; 87(12):4879-4883.
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  23. Chen PY, Hou CW, Shibu MA, Day CH, Pai P, Liu ZR, Lin TY, Viswanadha VP, Kuo CH, Huang CY: Protective effect of Co-enzyme Q10 On doxorubicin-induced cardiomyopathy of rat hearts. Environ Toxicol 2016. doi: 10.1002/tox.22270
  24. Fouad AA, Al-Sultan AI, Refaie SM, Yacoubi MT: Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. Toxicology 2010; 274(1-3):49-56.
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  30. Rusciani L, Proietti I, Paradisi A, Rusciani A, Guerriero G, Mammone A, De GA, Lippa S: Recombinant interferon alpha-2b and coenzyme Q10 as a postsurgical adjuvant therapy for melanoma: a 3-year trial with recombinant interferon-alpha and 5-year follow-up. Melanoma Res 2007; 17(3):177-183.
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