Coenzyme Q10: A therapy for hypertension and statin-induced myalgia?
ABSTRACTSome small clinical trials seem to show that coenzyme Q10 supplements can be used to lower blood pressure and to treat or prevent myalgia caused by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). However, larger trials are needed to determine if they are truly effective for these purposes. The authors examine the evidence and also discuss issues such as bioavailability, elimination, safety, and cost.
KEY POINTS
- In some clinical trials, coenzyme Q10 supplements significantly lowered diastolic and systolic blood pressure.
- Statins may lower coenzyme Q10 serum levels, and some investigators have evaluated the relationship between coenzyme Q10 deficiency and statin-related myalgia, but more evidence is needed to support the use of coenzyme Q10 supplements to prevent or treat myalgia.
- Coenzyme Q10 supplementation appears to be relatively safe. Most clinical trials have not reported significant side effects that necessitated stopping therapy. Gastrointestinal effects include abdominal discomfort, nausea, vomiting, diarrhea, and anorexia. Allergic rash and headache have also been reported.
STUDIES IN STATIN-INDUCED MYOPATHY
Thibault et al32 and Kim et al33 reported that patients taking lovastatin (Mevacor) at dosages as high as 35 mg/kg/day to inhibit tumor growth achieved symptomatic relief of statin-induced musculoskeletal toxicity after coenzyme Q10 supplementation.
Caso et al15 performed a small pilot study in 32 patients to determine if coenzyme Q10 supplementation would improve myalgic symptoms in patients treated with statins. In this double-blind, randomized trial, patients received either coenzyme Q10 100 mg/day or vitamin E 400 IU/day for 30 days. The extent of muscle pain and its interference with daily activities were determined before and after therapy using the Brief Pain Inventory Questionnaire. The statins were atorvastatin (Lipitor) 10 mg or 20 mg, lovastatin 40 mg, pravastatin 40 mg, and simvastatin 10, 20, 40, and 80 mg. Five patients in the coenzyme Q10 group and four patients in the vitamin E group were taking nonsteroidal anti-inflammatory drugs before and during the trial. The intensity of muscle pain and its interference with daily activities were similar between study groups before the start of therapy.
After 30 days of treatment with coenzyme Q10, the pain intensity had decreased significantly from baseline (P < .001). In contrast, no change in pain intensity from baseline was noted in patients receiving vitamin E. The Pain Severity Score was significantly different between study groups, favoring the coenzyme Q10 group (P < .001). Sixteen of 18 patients on coenzyme Q10 reported a reduction in pain, while only 3 of 14 patients on vitamin E reported a similar response. Also, the interference of pain with daily activities significantly improved with coenzyme Q10 (P < .02), whereas vitamin E did not have a significant impact on this.
Young et al17 randomized 44 patients with prior statin-induced myalgia to receive increasing doses of simvastatin (10–40 mg/day) in combination with either coenzyme Q10 (Q-Gel) 200 mg/day or placebo. The primary goal was to determine if coenzyme Q10 supplementation would help improve statin tolerance in patients with a history of statininduced myalgia. Plasma coenzyme Q10 and lipid levels were measured at baseline and at the end of the study. The intensity of myalgia was assessed with a visual analogue scale.
At 12 weeks, the coenzyme Q10 plasma level was significantly higher in the treatment group than in the placebo group (P < .001). However, no differences were noted between groups in the number of patients who tolerated the 40-mg/day simvastatin dose (P = .34) or in the number of patients who remained on any simvastatin dose (P = .47). Additionally, myalgia scores did not differ between groups (P = .63). The authors acknowledged that there were only small increases in the myalgia pain scores reported in either group. Therefore, patients in the treatment group may not have experienced sufficiently severe muscle pain to have benefited from coenzyme Q10 supplementation.
IS COENZYME Q10 SAFE?
Studies have indicated that these supplements are well tolerated, with relatively few adverse effects or potential drug interactions.1,2,34
The FDA does not routinely assess the purity or quality of over-the-counter coenzyme Q10 products.35 However, the United States Pharmacopeia (USP) does test dietary supplements to make sure that they are not mislabeled and that they do not contain contaminants. 36
A USP-verified dietary supplement should:
- Contain the exact ingredients listed on the label in the listed potency and amounts
- Not include harmful levels of certain contaminants such as lead, mercury, pesticides, or bacteria
- Appropriately disintegrate and release its contents into the body within a specified period of time
- Be produced using the FDA’s current Good Manufacturing Practices.36
Side effects, contraindications, warnings
Coenzyme Q10 is a relatively safe dietary supplement. It is contraindicated in patients who are allergic to it or to any of its components.2 Most clinical trials have not reported significant adverse effects that necessitated stopping therapy.34 However, gastrointestinal effects such as abdominal discomfort, nausea, vomiting, diarrhea, and anorexia have occurred.1,2,34 Allergic rash and headache have also been reported.1,2,34 In addition, coenzyme Q10’s antiplatelet effect may increase the risk of bleeding. 37,38 It undergoes biotransformation in the liver and is eliminated primarily via the biliary tract,39 so it can accumulate in patients with hepatic impairment or biliary obstruction.
Interactions with drugs
Coenzyme Q10’s effects on platelet function may increase the risk of bleeding in patients taking antiplatelet drugs such as aspirin or clopidogrel (Plavix).37,38 On the other hand, since it acts like vitamin K, it may counteract the anticoagulant effects of warfarin (Coumadin). 1,2,40
Coenzyme Q10 may have an additive antihypertensive effect when given with antihypertensive drugs.41
Coenzyme Q10 may improve beta-cell function and enhance insulin sensitivity, which may reduce insulin requirements for diabetic patients.42,43
SLOWLY ABSORBED
Coenzyme Q10 is absorbed slowly from the gastrointestinal tract, possibly because it has a high molecular weight and is not very watersoluble. 39
One pharmacokinetic study found that after a single 100-mg oral dose of coenzyme Q10, the mean peak plasma levels of about 1 μg/mL occurred between 5 and 10 hours (mean 6.5 hours).44 Coenzyme Q10 100 mg given orally three times daily produced a mean steadystate plasma level of 5.4 μg/mL; about 90% of this steady-state concentration was achieved after 4 days.39
Some formulations have significantly better oral bioavailability and therefore produce higher plasma levels. Soft-gel capsules, especially those with vegetable oil or vitamin E, may have better absorption.43
A pharmacokinetic study showed that the area under the curve of the plasma coenzyme Q10 concentration was more than twice as high with Q-Gel soft-gel capsules, a completely solubilized formulation, than with softgel capsules with an oil suspension, powderfilled hard-shell capsules, or regular tablets.45 Another study reported that colloidal-Q10, a formulation contained in VESIsorb (a novel drug delivery system sold as CoQsource) had greater bioavailability than solubilized and oil-based preparations.46 Commercially available solubilized preparations containing ubiquinol, a metabolized form of coenzyme Q10, have been shown to produce higher serum levels than solubilized products.47
Of note: unless the manufacturer claims that its product is water-soluble, the USP does not evaluate its dissolution rate.48 Therefore, USP-verified coenzyme Q10 products that are not water-soluble may have lower bioavailability than their solubilized counterparts.
Dry dosage forms of coenzyme Q10 (eg, tablets, capsules) may be more readily absorbed if taken with a fatty meal.43
