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A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy

Beth A Taylor, Lindsay Lorson, C Michael White, Paul D Thompson
Atherosclerosis 2015 238(2):329-335

Bibliography

PubMed
PMID 25545331
PubMed Central
PMC4298455
DOI
10.1016/j.atherosclerosis.2014.12.016
Funding
Supported by the National Center for Complementary and Alternative Medicine (NCCAM), NIH, grant 1RC1AT005836.
Competing interests
A specific conflict-of-interest statement for this original trial was not clearly identified in the accessible full-text excerpt checked during this audit; no conflict is inferred. Later publications from the investigative group contain author-specific disclosures, but those are not substituted for this paper.

Study snapshot

DesignRandomized double-blind placebo-controlled trial after blinded statin-myalgia confirmation phase
ModelTwo-stage randomized, double-blind study: an 8-week simvastatin-versus-placebo crossover confirmation phase in patients reporting prior statin myalgia, followed by a randomized CoQ10 treatment phase only in participants with objectively confirmed statin-associated myalgia.
Sample120 entered the confirmation crossover phase; 41 (36%) developed pain on simvastatin but not placebo and entered the treatment phase. In the main parallel treatment comparison, 20 received CoQ10 and 18 placebo with simvastatin; 24 later completed both CoQ10 and placebo treatment arms in crossover follow-up.
InterventionAfter a 2-week loading period, ubiquinol 600 mg/day or matching placebo was continued while participants received simvastatin 20 mg/day for up to 8 weeks.
DurationConfirmation: two 8-week simvastatin/placebo periods separated by washout. Treatment: 2-week CoQ10/placebo loading followed by up to 8 weeks with simvastatin; a subset crossed over to the alternate treatment.
EndpointsBrief Pain Inventory pain severity; Pain interference; Time to muscle-pain onset; Arm and leg muscle strength; VO2max; Creatine kinase; Serum CoQ10; Proportion reporting muscle pain; Confirmed statin myalgia during lead-in

What the study showed, in plain terms

This trial used an unusually rigorous design for statin-associated muscle symptoms. Of 120 people who believed they had statin myalgia, only 41 developed muscle pain on blinded simvastatin 20 mg/day but not on placebo during the confirmation phase; only those confirmed cases entered the CoQ10 treatment study.

Ubiquinol 600 mg/day produced a large rise in serum CoQ10—from 1.3 ± 0.4 to 5.2 ± 2.3 µg/mL—but did not reduce pain severity, pain interference, time to pain onset, muscle strength loss or aerobic-performance changes relative to placebo. Pain actually occurred numerically more often with CoQ10: 14/20 (70.0%) versus 7/18 (38.8%), p=0.05.

The same null pattern appeared in the 24 participants who later received both treatments. Because the study confirmed statin causality before testing CoQ10 and documented strong biochemical exposure, it is particularly important negative evidence against using CoQ10 as a reliably effective treatment for true statin myalgia.

Key findings

Diagnostic confirmation: only 41/120 participants with a history of statin myalgia developed pain on simvastatin but not placebo during the blinded crossover lead-in—approximately 36%.

Serum exposure: CoQ10 rose from 1.3 ± 0.4 to 5.2 ± 2.3 µg/mL with ubiquinol, while placebo/simvastatin changed from 1.3 ± 0.3 to 0.8 ± 0.2 µg/mL (p<0.05 between groups).

Pain severity and interference increased during simvastatin regardless of CoQ10 assignment; treatment-by-time interactions were p=0.53 and p=0.56, respectively.

Muscle pain at treatment end: 14/20 (70.0%) with CoQ10 vs 7/18 (38.8%) with placebo; p=0.05. Time to pain onset: 3.0 ± 2.0 vs 2.4 ± 2.1 weeks; p=0.55.

Muscle strength, CK and VO2max: no significant CoQ10 benefit (all reported p>0.10 for performance outcomes).

Crossover subset: among 24 participants receiving both treatments, there were again no significant differences in pain or performance; 17/24 reported pain on CoQ10 versus 13/24 on placebo (p=0.23).

Trial registration: NCT01140308.

What this study can and cannot tell us

The treatment phase was small because only 41 of 120 self-reported cases met the blinded confirmation definition; this improves diagnostic specificity but reduces precision.

The confirmation sequence showed a possible order effect: participants randomized to simvastatin first were more likely to meet the myalgia-confirmation definition than those receiving placebo first, highlighting complexity in symptom attribution.

The study tested simvastatin 20 mg/day and high-dose ubiquinol 600 mg/day; results do not prove that every statin, formulation or lower-dose CoQ10 regimen is ineffective, although they strongly argue against a robust class-wide therapeutic effect.

The trial assessed symptom treatment rather than prevention before first statin exposure or long-term statin adherence in broader populations.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology