Description
Coenzyme Q10 (CoQ10) is a naturally occurring antioxidant produced by the body. CoQ10 is utilised by cells for growth and maintenance. As CoQ10 is produced naturally in the body, CoQ10 deficiency is rare in the healthy population. Nevertheless, CoQ10 supplements are widely used and have been studied for various health indications. Research on CoQ10 has focused primarily on cardiovascular disease, although it has also been used in the context of cancer for chemotherapy-induced cardiotoxicity, cancer-related fatigue, inflammation and anti-tumour effects. The underlying mechanisms of action are thought to be antioxidant, immunomodulatory and possible anti-inflammatory.
Efficacy
Four systematic reviews and three randomized controlled trials (RCTs) not included in these reviews are available.
Supportive care
Treatment-related cardiotoxicity: Three of five controlled clinical trials (CCTs) included in a SR reported positive effects on surrogate parameters of cardiac function, all studies were of high risk of bias.
Fatigue: In a SR of two RCTs in breast cancer patients, one RCT (n=236) of CoQ10 reported no improvements of fatigue while one RCT (n=59) of a combination product containing CoQ10 suggested some improvements.
Inflammation: One SR (n=3 RCTs) reports anti-inflammatory effects of CoQ10 in liver and breast cancer patients (low-certainty evidence).
Antitumour treatment
Tumour recurrence: One CCT (n=80) reported a significantly reduced risk of developing metastases in melanoma patients receiving CoQ10 + interferon vs interferon alone (CCT=80, low-certainty evidence).
PSA levels: there is conflicting evidence from two RCTs (n=79, n=49) of CoQ10 combination products (low-certainty evidence).
Safety
CoQ10 is generally safe and well tolerated when taken as a dietary supplement. In cancer care, there is some concern regarding its use before and during chemotherapy in breast cancer populations based on one observational study, which reported that the use of coenzyme Q10 (standalone or in combination with vitamins C, E) was associated with a non-significantly increased hazard of breast cancer recurrence.
Citation
Pawel Posadzki, CAM Cancer Collaboration. Coenzyme Q10 [online document], June 2024.
Document history
Most recent revision and update in 2023 by Pawel Posadzki and the CAM Cancer Collaboration.
Revised and updated in June 2016 by Mario Rottorf. Assessed as up to date in April 2014 by Barbara Wider. Fully revised and updated in December 2012, September 2011 and August 2009 by Helen Cooke. First published in 2005, authored by Helen Seers and Helen Cooke.
Description
CoQ10 is a naturally produced molecule that is found in the membranes of nearly all of the body’s cells. Concentrations are particularly high in the inner mitochondrial membrane (da Silva 2013). CoQ10 is structurally related to vitamins K and E. Its structure is what gives CoQ10 its name: the "Q" refers to the molecule's quinone structure, while the "10" refers to the lipophilic isoprenoid chain of 10 subunits (NCI 2016). The term "ubiquinone" is frequently employed to describe CoQ10, furthermore it is referred to as Vitamin Q10, ubiquinol, ubidecarenon, mitoquinone, adelir, heartcin, neuquinone, and taidecanone. (Garrido-Maraver 2014)
Background
CoQ10 was first isolated in 1957 and then described as a benzoquinone structure one year later (Folkers 1997, Pepping 1999). It is also available as a dietary supplement, made by microbial fermentation (Cluis 2012), and is mainly used in cardiovascular disease. Interest in CoQ10 as an agent in cancer care began in the 1960s when studies found lower serum concentrations of CoQ10 in a variety of cancers (NCI 2016).
Ingredients and quality issues
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 (da Silva 2013). The quality and composition of CoQ10 products may differ between manufacturers (Overvad 1999, ConsumerLab.com 2023).
Alleged indications
CoQ10 has been mainly investigated for its use in cardiovascular disease (Al Saaidi 2021; Sui-Ling 2022). Other clinical applications include migraine, fatigue, neurogenerative diseases such as Parkinson’s, Alzheimer, multiple sclerosis as well as neuropathy and cancer (Testai 2021).
In the context of cancer, CoQ10 has been purported to have anticancer effects, both as a preventative and treatment agent. (NCI 2016) It has also been reported to support treatment-related side effects such as fatigue and cardiotoxicity.
Application and dosage
Dietary intake of CoQ10 is only 3-10mg/d; the body meets 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 deficiency (Lesser 2013, Potgieter 2013, Kaikkonen 1999, Overvad 1999). The reference range of the CoQ10 concentration in serum/whole blood lies between 433-1,532 mcg/L for adults (HealthMatters 2023).
CoQ10 is sold as a dietary supplement and usually taken orally as a capsule or tablet. It can also be administered intravenously. There are challenges in absorbing Co10 from dietary supplements and different products have yielded different results (López-Lluch 2019). Due to its lipophilic nature, CoQ10 is absorbed more effectively when taken with high-fat foods. Consequently, intravenous CoQ10 is available as lipid preparations (NCI 2016). Typical doses range from 60-1000mg per day for up to 12 weeks. (NatMed 2023) Dosages of 50-3000 mg/day have been used in clinical studies.
Mechanism of action
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 and anti-inflammatory properties have been discussed on the basis of experimental and epidemiological data.
Legal issues
CoQ10 is a nutritional supplement and can be purchased over the counter.
Four systematic reviews (SRs) evaluating the effects of CoQ10 on a range of outcomes such as health-related quality of life, antitumour treatment, and treatment-related adverse effects, are available. (Alimohammadi 2021; Arring 2019; Tafazoli 2017; Roffe 2004). The most recent three SRs were published between 2017 and 2021.
The Tafazoli 2017 narrative review aimed to evaluate the effects of CoQ10 on a range of outcomes and included all studies from in vitro to clinical. It included the same RCTs as the more recent SRs mentioned above, but the authors did not report quantitative findings; hence its findings cannot be meaningfully interpreted.
The SRs are described below and in table 1. The SRs all suffered methodological shortcomings including considerable heterogeneity, high risk of bias of the primary studies, which adds to the considerable uncertainty about any therapeutic effects. Further RCTs investigated PSA levels (n=2) and tumour recurrence (n=1) (included in SRs by Grammatikopoulou 2020 and Hackshaw 2015).
Description of included studies
Supportive care
Treatment-related cardiotoxicity
A systematic review analysed the issue of whether oral administration of CoQ10 improved the tolerability of chemotherapy and reduced adverse events and toxicity (Roffe 2004). 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.
Fatigue
The SR by Arring 2019 evaluated the effects of integrative therapies for cancer-related fatigue and included two RCTs of CoQ10 (one thereof a combination product with amino acids and L-carnitine) in breast cancer patients.
The first RCT assessed 236 women with newly diagnosed breast cancer and planned adjuvant chemotherapy who were randomized to oral supplementation of 300-mg CoQ10 or placebo, each combined with 300-IU vitamin E, divided into 3 daily doses. There were no significant differences between the CoQ10 and placebo arms at 24 weeks for fatigue scores (Lesser 2013).
The second RCT aimed to investigate the efficacy of Inner Power®, containing branched-chain amino acids (2500mg) coenzyme Q10 (30mg) and L-carnitine (50mg) in controlling cancer-related fatigue in 59 breast cancer patients (Iwase 2016). The authors reported that compared with usual care (recommendations for exercise and relaxation), the supplement reduced the worst level of fatigue but had no effect on the average feeling of fatigue.
Inflammation
The SR by Alimohammadi 2021 evaluated the effects of CoQ10 on serum levels of various inflammatory markers in the large and relatively homogenous sample of breast cancer participants undergoing tamoxifen therapy. The SR included results from 2 RCTs (1 RCT thereof is reported in 4 papers; total number of participants is unclear due to double counting). The SR found some evidence for altered immune function/biomarkers of inflammation such as reductions in vascular endothelial growth factor, interleukin-8, matrix metalloproteinase-2 or matrix metalloproteinase-9; and no effect on tumour necrosis factor-α, interleukin-6, interleukin-1β, catalase, superoxide dismutase, glutathione peroxidase, glutathione, or thiobarbituric acid reactive substances.
One RCT not included in the above SRs (Liu 2016) evaluated effectiveness of various doses of CoQ10 compared with placebo in reducing markers of inflammation in 41 participants with hepatocellular cancer. It reported significantly decreased levels of oxidative stress and inflammatory markers as well as increased antioxidant enzymes activity after 12 weeks of supplementation with 300mg/day of coenzyme Q10.
Antitumour treatment
Tumour recurrence
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 therapy (Rusciani 2007). In the CoQ10 treatment group, the recurrence rate was significantly lower after 5 years of follow-up. The risk of developing metastases was about 10 times lower in IFN+CoQ10 group compared with the IFN group (95% CI: 0.0020–0.6732). Odds ratios computed for stage II vs. stage I and for IFN+CoQ10 vs. IFN therapy were 14.32 (95% CI: 1.7090–120.0029) and 0.078 (95% CI: 0.0093–0.6569), respectively, indicating that the risk of metastasis increased with rising disease stage, and that therapy with IFN+CoQ10 reduced this risk. However, the results are at high risk of bias due to the lack of randomisation and the small patient sample.
PSA Levels
Hoenjet 2005 evaluated the effects of CoQ10 (200mg) in combination with vitamin E (350 mg), Selenium (200 μg), vitamin C (750 mg) over a period of 21 weeks in a sample of 70 prostate cancer patients (N=70) after radical prostatectomy or curative radiotherapy, or without curative treatment. The authors reported that compared with placebo the intervention had no effect on serum PSA concentrations.
Schroder 2005 evaluated the effects of CoQ10 (4mg) in combination with soy (62.5 mg), lycopene (15 mg), and selenium (128 mg) in an RCT of 49 patients with a history of prostate cancer and rising prostate-specific antigen (PSA) levels. The authors reported that compared with placebo the intervention delayed PSA progression.
Adverse effects
CoQ10 is generally well tolerated. Adverse events are rare; they are mild and transient mainly affecting the gastrointestinal tract. No serious adverse events have reported in clinical trials. (NatMed 2023). Two reviews of preclinical and clinical data concluded that CoQ10 is safe as a dietary supplement (Hatchcock 2006; Hidaka 2008), the more recent SRs do not report on safety issues. The observed safety level (OSL) is 1200 mg/day, and oral administration for up to 30 months is regarded as safe. (Hatchcock 2006). In children, a maximum daily dose of 10mg/kg body weight is considered safe; in pregnant women, a maximum daily dose of 200mg/day is considered safe (NatMed 2023).
Contraindications
There are no known contraindications for CoQ10 supplements (NatMed 2023).
Interactions
Theoretically, CoQ10’s antioxidant mechanism of action could impact the efficacy of some chemotherapeutic agents (such as anthracycline and cyclophosphamide) as well as radiotherapy. One observational study conducted with 1,134 patients with breast cancer enrolled in a National Cancer Institute multi-institution clinical trial suggested that the use of antioxidants including coenzyme Q10 (standalone or in combination with vitamins C, E) before and during chemotherapy may be associated with an increased hazard of breast cancer recurrence; and reduced overall survival (although statistically not significant), (Ambrosone 2020).
Although there are individual case reports which suggest that CoQ10 can reduce the efficacy of coumarins (Spigset 1994, Heck 2000, Porterfield 2000), a phenomenon that can be explained by the structural similarity between CoQ10 and Vitamin K (NCI 2016), a small 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 weeks (Engelsen 2003).
Taking CoQ10 can lower the need for insulin in patients with diabetes (Pepping 1999, Kaikkonen 1999) and CoQ10’s might have hypotensive effects which should be taken into account in antihypertensive treatment (NatMed 2023).
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