Herb-Drug Interactions: Coenzyme Q10

Types, sources and related compounds

Ubidecarenone, Ubiquinone.

Pharmacopoeias

Ubidecarenone (British Ph 2009, European Ph 2008, US Ph 32); Ubidecarenone Capsules (US Ph 32); Ubidecarenone Tablets (The United States Ph 32).

Use and indications

Coenzyme Q10 is a naturally occurring enzyme co-factor that has a fundamental role in electron transport in mitochondria, and is also an antioxidant. It is often taken orally as a supplement to aid in the treatment of cardiovascular disorders such as congestive heart failure, angina and hypertension. It has also been used to maintain the levels of endogenous coenzyme Q10 during treatment with conventional drugs that reduce these, particularly the statins. Coenzyme Q10 has also been used alongside treatment for breast cancer, Huntington’s disease and Parkinson’s disease, and may help to prevent migraines.

Pharmacokinetics

The absorption of coenzyme Q10 is relatively slow and is dependent on postprandial lipids in the gastrointestinal tract, see food.

Interactions overview

Coenzyme Q10 did not interact with warfarin in a controlled study, but there are a few isolated reports describing either increased or decreased warfarin effects in patients taking coenzyme Q10. Coenzyme Q10 may decrease the effects of aldosterone and alter the levels of the major cytotoxic metabolite of doxorubicin. Pepper (Piper nigrum) may modestly increase the levels of coenzyme Q10.

Coenzyme Q10 + Aldosterone

The interaction between coenzyme Q10 and aldosterone is based on experimental evidence only.

Evidence, mechanism, importance and management

In experimental studies in rats and dogs, single-dose coenzyme Q10 increased the sodium reabsorption stimulated by exogenous aldosterone, but, in contrast, in rats and dogs pretreated for 3 weeks with multiple doses, increasing the dose of coenzyme Q10 reduced the sodium reabsorption caused by aldosterone. Potassium excretion remained unaffected throughout.

This study suggests that long-term use of coenzyme Q10 might have some diuretic activity, and might oppose the effects of aldosterone. However, the clinical relevance of this is uncertain.

Coenzyme Q10 + Doxorubicin

The interaction between coenzyme Q10 and doxorubicin is based on experimental evidence only.

Evidence, mechanism, importance and management

In a study in rats, oral coenzyme Q10 20mg/kg for 6 days had no significant effect on the pharmacokinetics of intravenous doxorubicin 10 mg/kg or its major cytotoxic metabolite doxorubicinol. However, there was a twofold increase in the AUC of the doxorubicinolone metabolite. The findings from this study suggest that coenzyme Q10 is unlikely to reduce the efficacy of doxorubicin via a pharmacokinetic mechanism. The reason for the significant rise in doxorubicinolone concentration and its impact is unknown. Note that the possible use of coenzyme Q10 to reduce doxorubicin-induced cardiotoxicity has been investigated.

Coenzyme Q10 + Food

The interaction between coenzyme Q10 and food is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

Food increased the maximum serum levels and AUC of oral coenzyme Q10 25mg/kg, given as an emulsion, by about fivefold and twofold respectively in rats. Coenzyme Q10 given as an emulsion showed greater increases than coenzyme Q10 given in suspension.

Mechanism

Coenzyme Q10 has a large molecular weight and is relatively hydrophobic, which results in slow absorption in the gastrointestinal tract. Taking the supplement with food and/or as a lipid-based emulsion increases its water solubility and enhances its absorption.

Importance and management

Data regarding the effects of food on coenzyme Q10 absorption appear to be limited. The absorption of coenzyme Q10 is relatively slow and is dependent on postprandial lipids in the gastrointestinal tract. Coenzyme Q10 supplements therefore often contain a lipid vehicle and it is recommended that they are taken with fatty meals.

Coenzyme Q10 + Herbal medicines; Pepper

Pepper (Piper nigrum) may modestly increase the levels of coenzyme Q10.

Clinical evidence

In a single-dose, placebo-controlled study in 12 healthy subjects, there was no change in pharmacokinetics of coenzyme Q10 (AUC and maximum level or time to maximum level) when piperine 5 mg (Bioperine) from pepper (Piper nigrum) was given with coenzyme Q10 90 mg. Similarly, giving piperine 5mg with coenzyme Q10 90 mg daily for 14 days did not alter the AUC of coenzyme Q10. However, when piperine 5mg was given with coenzyme Q10 120 mg daily for 21 days, the plasma levels of coenzyme Q10 were increased by 32% and the AUC was increased by 30%.

Experimental evidence

No relevant data found.

Mechanism

It was suggested that piperine increased the absorption of coenzyme Q10 from the gastrointestinal tract, but the exact mechanism is unclear.

Importance and management

The modest increase in coenzyme Q10 levels seen in this study with piperine (an alkaloid derived from black pepper) is unlikely to be clinically important, since coenzyme Q10 is a ubiquitous compound, generally regarded as safe. Note that a combination product has been marketed.

Coenzyme Q10 + Warfarin and related drugs

Ubidecarenone did not alter the INR or required warfarin dose in a controlled study in patients stabilised on warfarin. However, two reports describe reduced anticoagulant effects of warfarin in four patients taking ubidecarenone. A transient increase in INR has been reported in one patient taking ubidecarenone and warfarin. A 4-month prospective, longitudinal study describes an increased risk of self-reported beeding events in patients taking coenzyme Q10 with warfarin.

Clinical evidence

In a randomised, crossover study in 21 patients stabilised on warfarin, coenzyme Q10 100 mg daily (Bio-Quinone) for 4 weeks did not alter the INR or the required dose of warfarin, when compared with placebo. Similarly, 2 patients taking coenzyme Q10 to treat alopecia caused by warfarin treatment did not have any notable changes in INR, except that one had a transient INR increase when coenzyme Q10 was started.

In a 4-month prospective, longitudinal study of 78 patients taking warfarin and a herbal product or dietary supplement, there was a statistically significant increased risk of self-reported bleeding events in 14 patients taking warfarin and coenzyme Q10 (57 bleeding events, none major, in a total of 181 weeks of combined use for an odds ratio of 3.7). There were 4 elevated INRs (specific values not given) for 55 weeks of combined use, but this was not a statistically significant increase in risk. Note that the coenzyme Q10 products used were not mentioned. The authors acknowledge that their finding might be due to chance and not a true interaction.

In contrast, another report describes 3 patients taking warfarin who had a reduction in their INR while taking coenzyme Q10. In two of these, INR reductions from about 2.5 to 1.4 occurred when they took coenzyme Q10 30 mg daily for 2 weeks. The INRs rapidly returned to normal when the coenzyme Q10 was stopped. In two other cases, patients appeared to have a reduced response to warfarin while taking coenzyme Q10, but responded normally when it was stopped.

Experimental evidence

In a study in rats, coenzyme Q10 reduced the anticoagulant effect of warfarin and increased the clearance of both enantiomers of warfarin.

Mechanism

Not known. Coenzyme Q10 may have some vitamin K-like activity, which would explain the decrease in INR. Explanations for the increase in bleeding or INRs are unknown.

Importance and management

The well-controlled study suggests that coenzyme Q10 does not interact with warfarin, and that no warfarin dose adjustment would be expected to be necessary in patients who take this substance. However, the contrasting findings of a decrease in warfarin effect in the case reports, and an increase in bleeding events reported in the epidemiological study, introduce a note of caution. Moreover, the authors of the controlled study recommend close monitoring of the INR if a patient decides to use coenzyme Q10, because the underlying health problem resulting in them choosing to take this substance may alter their response to warfarin. Until more is known it would seem prudent to increase the frequency of INR monitoring in patients taking warfarin if coenzyme Q10 is started.