Coenzyme Q10 supplementation for the treatment of statin-associated muscle symptoms (2024)

Abstract

Aim:

To determine the association of coenzyme Q10 (CoQ10) use with the resolution of statin-associated muscle symptoms (SAMS).

Patients & methods:

Retrospective analysis of a large, multicenter survey study of SAMS (total n=511; n=64 CoQ10 users). Univariate and multivariate logistic regression models assessed the association between CoQ10 use and the resolution of SAMS.

Results:

The frequency of SAMS resolution was similar between CoQ10 users and non-users (25% vs 31%, respectively; unadjusted odds ratio [OR]: 0.75 [95% CI: 0.41–1.38]; p=0.357). Similarly, CoQ10 use was not significantly associated with the resolution of SAMS in multivariable models adjusted for SAMS risk factors (OR: 0.84 [95% CI: 0.45–1.55]; p=0.568)or adjusted for significant differences among CoQ10 users and non-users (OR: 0.82 [95% CI: 0.45–1.51]; p=0.522).

Conclusion:

CoQ10 was not significantly associated with the resolution of SAMS.

Keywords: : cardiology, cardiovascular diseases, coenzyme Q10, humans, hydroxymethylglutaryl-CoA reductase inhibitors, retrospective studies, risk factors

Plain language summary

Statins are medications that help lower cholesterol and treat cardiovascular disease, but muscle pain is the most common side effect of statins. Statins decrease the body's levels of coenzyme Q10 (CoQ10), and thus taking CoQ10 supplements (which are widely available over the counter in pharmacies) may help treat the muscle side effects from statins. However, the results of previous studies are not clear whether CoQ10 is effective for treating statin-associated muscle symptoms. Therefore, the purpose of this study was to analyze whether the use of CoQ10 supplements improved statin-associated muscle side effects in a large group of individuals. When the authors compared the survey responses of 64 CoQ10 users versus those of 447 non-CoQ10 users with statin-associated muscle symptoms, CoQ10 supplements did not improve their muscle symptoms.

Tweetable abstract

Coenzyme Q10 supplements do not improve statin-associated muscle symptoms or the continuation of statin therapy in patients with a history of statin-associated muscle symptoms.

One in four Americans over the age of 39 yearstake a statin [1]. Statins are highly effective for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) [2], and they are usually well tolerated. However, their usage may also lead to adverse muscle effects, ranging from mild muscle symptoms to myopathy, and rarely to life-threatening rhabdomyolysis. In observational studies, statin-associated muscle symptoms (SAMS) occurred in 5–20% of patients [3,4], and SAMS are the number one reason for statin non-adherence and discontinuation [5]. A variety of options are available to treat SAMS, such as changing to a different statin, rechallenging with the same statin, reducing the dosage of the statin, using intermittent statin dosing, changing to a non-statin cholesterol-lowering drug (e.g., ezetimibe) and adding supplemental coenzyme Q10 (CoQ10). However, the most effective option for treating SAMS, while maintaining maximum protection against ASCVD, has yet to be determined.

Supplemental CoQ10 is a highly attractive option for treating SAMS for several reasons. By inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, statins not only decrease cholesterol synthesis but also significantly decrease the synthesis of CoQ10 [6,7]. Indeed, significantly decreased levels of CoQ10 in muscle and serum have been reported with statin therapy [6]. The current cholesterol treatment guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) recommend that patients be treated with certain intensities of statin therapy to adequately protect against ASCVD [2]. Adding CoQ10 to statin therapy is a more attractive option for treating SAMS than statin dose reductions or alternative cholesterol-lowering drugs, because it would allow patients to remain on the guideline-recommended intensity of statin therapy, thereby providing maximum protection against ASCVD. Moreover, CoQ10 is widely available over the counter, is taken orally and costs as low as $7 per month out of pocket (200mg/day). CoQ10 has also been shown to provide other types of benefits in patients with hyperlipidemia, such as significantly improved levels of inflammatory markers, lipid levels and blood pressure [8,9]. PCSK9 inhibitors are a new, non-statin alternative that achieves even greater cholesterol lowering than statins [2]. However, the high cost of those drugs, and the fact that they are only available as an injection, eliminates them as an option for many patients [2]. Rechallenging with the same statin, or even trying a different statin, also may not be an option for some patients. After initially experiencing SAMS, some patients refuse rechallenge with the same statin or even a different statin [5]. The effectiveness of CoQ10 for treating SAMS is still unclear [10–13]. Therefore, the primary objective of this study was to determine whether CoQ10 use is associated with the resolution of SAMS. The secondary objective was to determine whether CoQ10 use is associated with continued statin use despite a history of SAMS.

Patients & methods

Multicenter SAMS study

This study is a retrospective analysis of one of the largest observational studies of SAMS to date [14–16]. The methods of the original study were previously published in detail [14–16]. Briefly, SAMS were defined as any symptoms specific to muscle that participants associated with the onset of statin therapy and included muscle symptoms (e.g., pain, weakness, cramps) and/or elevated creatine kinase (CK) levels. SAMS cases were enrolled from six medical centers across the USA and Canada between 2004 and 2013: the University at Buffalo, John Hopkins Myositis Center, Cedars-Sinai Medical Center, the Medical College of Wisconsin, McMaster University Medical Center and the University of OklahomaCollege of Medicine. Patients completed detailed questionnaires at baseline and after 12 months of follow-up on their current SAMS symptoms, comorbid conditions and medication list (see Supplemental Material for questionnaire). Nurses and research coordinators at each site assisted participants in completing the questionnaires. The study was approved by the institutional review boards at each participating study site, and all participants provided written informed consent.

Individuals were included in this specific analysis if they stated having had SAMS in the past 5 years. The original study had 634 SAMS cases [15], but it included both patients with SAMSin the past and those with current SAMS (at the time of the survey but not in the past), whereas this study could only include patients who had had SAMS in the past 5 yearsbecause the outcome was evaluating the resolution of SAMS at the time of the survey.

Statistical analysis

The primary outcome was binary: whether or not the participants had resolution of SAMS (i.e., they reported experiencing SAMS in the past 5 years, but they no longer reported any SAMS at the current time of completing the questionnaire). The secondary outcome was also binary: whether or not the participants that experienced SAMS in the past continued to take any statin currently. Baseline statistics for demographic and clinically relevant characteristics were calculated in all participants and stratified by the resolution of SAMS over the past 5 years (the primary outcome) and by CoQ10 use. Continuous variables were compared between the two groups by Student's t-tests (if normally distributed by Kolmogorov–Smirnov test and visual inspection of distribution plots) or Mann–Whitney test (if not normally distributed). Categorical variables were compared using chi-square tests or Fisher's exact tests where necessary.

Univariate and multivariate logistic regression models were used to assess the association between CoQ10 use and the primary and secondary outcomes. Drug–drug interactions that could increase or decrease statin exposure, and hence influence the occurrence of SAMS in participants, were assessed in the original study [15]. There was no significant difference in the number of medications that could impact statin exposure (i.e., CYP3A4 inducers/inhibitors) between those experiencing SAMS and controls. Thus, drug–drug interactions were excluded from this analysis. Model 1 is the univariate model. Model 2 includes the five baseline characteristics that were associated with SAMS in the original study as covariates: obesity, family history of heart disease, hypertension, smoking and the specific statin used when the SAMS occurred [15]. Model 3 includes the three baseline characteristics that were significantly different between the CoQ10 users and non-users as covariates: smoking, obesity and family history of muscle disease. Based on this sample size, the authors estimatedhaving 80% power to detect an odds ratio (OR) of 2.5for CoQ10 in the univariate model for the primary outcome. All of the data analysis was completed on SAS version 9.4 and p<0.05 was considered statistically significant.

Results

Of the original sample of 634 in the study who had SAMS [15], 511 participants met the inclusion criteria for this study. The baseline characteristics of all participants and stratified by CoQ10 usage are presented in Table1. The mean (± standard deviation) age of the participants was 58±11 years, with 54% males and 100% Caucasian. The participants had been on a wide range of statin types in the past, with the most common being atorvastatin (n=261; 51.1%). At the time of the survey, about half ofthe participants had discontinued cholesterol-lowering therapy (50.3%) or were taking a non-statin (16.2%). Overall, 29.9% of the participants had a resolution of SAMS (n=153), and overall, 64 participants were using CoQ10 (12.5%). CoQ10 users were significantly more likely to be smokers, to be obese and to have a family history of muscle disease compared with non-users of CoQ10. Table2 shows the baseline characteristics of all participants and stratified by whether or not the participants had a resolution of SAMS. There were no significant differences among the participants that did and did not have SAMS resolved, except for the specific statin used in the past (p=0.018) and their current cholesterol-lowering therapy (p<0.001).

Table 1.. Participant characteristics overall and stratified by coenzyme Q10 usage.

CharacteristicAll (n=511)On coenzyme Q10 (n=64; 12.5%)Not on coenzyme Q10 (n=447; 87.5%)p-value
Male sex276 (54.0%)38 (59.4%)238 (53.2%)0.357
Age started cholesterol-lowering drug (years)57.8±10.658.1±9.657.8±10.80.809
Past statin therapy (taken at the onset of SAMS):
  Atorvastatin261 (51.1%)38 (59.4%)223 (49.9%)0.770
  Simvastatin108 (21.1%)14 (21.9%)94 (21.0%)
  Rosuvastatin70 (13.7%)6 (9.4%)64 (14.3%)
  Pravastatin39 (7.6%)3 (4.7%)36 (8.1%)
  Lovastatin21 (4.1%)2 (3.1%)19 (4.3%)
  Other statin12 (2.3%)1 (1.6%)11 (2.5%)
Statin dose normalized to atorvastatin(mg)§23.0±22.622.7±20.223.1±23.00.641
Current cholesterol-lowering therapy (taken at the time of the survey):
  None257 (50.3%)30 (46.9%)227 (50.8%)0.233
  Non-statin83 (16.2%)12 (18.8%)71 (15.9%)
  Atorvastatin36 (7.1%)3 (4.7%)33 (7.4%)
  Simvastatin33 (6.5%)8 (12.5%)25 (5.6%)
  Rosuvastatin53 (10.4%)4 (6.3%)49 (11.0%)
  Pravastatin40 (7.8%)5 (7.8%)35 (7.8%)
  Lovastatin7 (1.4%)1 (1.6%)6 (1.3%)
  Other statin2 (0.4%)1 (1.6%)1 (0.2%)
Statin dose normalized to atorvastatin(mg)§7.1±16.86.1±13.97.3±17.20.971
Coronary artery disease108 (21.1%)19 (29.7%)89 (19.9%)0.073
Myocardial infarction68 (13.3%)13 (20.3%)55 (12.3%)0.078
Hypertension256 (50.0%)32 (50.0%)224 (50.1%)0.987
Smoker188 (36.8%)33 (51.6%)155 (34.7%)0.009
Family history of heart disease276 (54.0%)33 (51.6%)243 (54.4%)0.674
Hypothyroidism69 (13.5%)10 (15.6%)59 (13.2%)0.595
Heavy alcohol consumption14 (2.7%)1 (1.6%)13 (2.9%)1.000
Obesity103 (20.2%)20 (31.3%)83 (18.6%)0.018
Kidney disease11 (2.2%)2 (3.1%)9 (2.0%)0.636
Diabetes79 (15.5%)10 (15.6%)69 (15.4%)0.969
Family history of muscle disease32 (6.3%)8 (12.5%)24 (5.4%)0.047
Metabolic muscle disease15 (2.9%)0 (0.0%)15 (3.4%)0.236
Inflammatory muscle disease46 (9.0%)5 (7.8%)41 (9.2%)0.722
Liver disease13 (2.5%)1 (1.6%)12 (2.7%)1.000
SAMS resolved153 (29.9%)16 (25.0%)137 (30.7%)0.356

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Data are presented asn (%) or mean ± standard deviation.

Bold values represent p < 0.05.

Fisher's exact tests.

Other statins include cerivastatin, fluvastatin and pitavastatin.

SAMS: Statin-associated muscle symptoms.

Table 2.. Participant characteristics overall and stratified by resolution of statin-associated muscle symptoms.

CharacteristicAll (n=511)SAMS did not resolve (n=358; 70%)SAMS resolved (n=153; 30%)p-value
Male sex276 (54.0%)198 (55.3%)78 (51.0%)0.369
Age started cholesterol-lowering drug (years)57.8±10.658.0±10.657.4±10.70.604
Past statin therapy (taken at the onset of SAMS):
  Atorvastatin261 (51.1%)195 (54.5%)66 (43.1%)0.018
  Simvastatin108 (21.1%)74 (20.7%)34 (22.2%)
  Rosuvastatin70 (13.7%)47 (13.1%)23 (15.0%)
  Pravastatin39 (7.6%)26 (7.3%)13 (8.5%)
  Lovastatin21 (4.1%)8 (2.2%)13 (8.5%)
  Other statin12 (2.3%)8 (2.2%)4 (2.6%)
Statin dose normalized to atorvastatin(mg)§23.0±22.623.2±22.422.6±23.10.491
Current cholesterol-lowering therapy (taken at the time of the survey):
  None257 (50.3%)204 (57.0%)53 (34.6%)<0.001
  Non-statin83 (16.2%)44 (12.3%)39 (25.5%)
  Atorvastatin36 (7.1%)23 (6.4%)13 (8.5%)
  Simvastatin33 (6.5%)24 (6.7%)9 (5.9%)
  Rosuvastatin53 (10.4%)36 (10.1%)17 (11.1%)
  Pravastatin40 (7.8%)23 (6.4%)17 (11.1%)
  Lovastatin7 (1.4%)2 (0.6%)5 (3.3%)
  Other statin2 (0.4%)2 (0.6%)0 (0.0%)
Statin dose normalized to atorvastatin(mg)§7.1±16.86.8±16.87.9±16.60.778
Coronary artery disease108 (21.1%)82 (22.9%)26 (17.0%)0.134
Myocardial infarction68 (13.3%)50 (14.0%)18 (11.8%)0.502
Hypertension256 (50.0%)188 (52.5%)68 (44.4%)0.095
Smoker188 (36.8%)135 (37.7%)53 (34.6%)0.510
Family history of heart disease276 (54.0%)189 (52.8%)87 (56.9%)0.398
Hypothyroidism69 (13.5%)54 (15.1%)15 (9.8%)0.110
Heavy alcohol consumption14 (2.7%)9 (2.5%)5 (3.3%)0.768
Obesity103 (20.2%)78 (21.8%)25 (16.3%)0.160
Kidney disease11 (2.2%)9 (2.5%)2 (1.3%)0.519
Diabetes79 (15.5%)61 (17.0%)18 (11.8%)0.131
Family history of muscle disease32 (6.3%)25 (7.0%)7 (4.6%)0.304
Metabolic muscle disease15 (2.9%)12 (3.4%)3 (2.0%)0.569
Inflammatory muscle disease46 (9.0%)32 (8.9%)14 (9.2%)0.939
Liver disease13 (2.5%)12 (3.4%)1 (0.7%)0.121
Coenzyme Q1064 (12.5%)48 (13.4%)16 (10.5%)0.356

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Data are presented as n (%) or mean ± standard deviation.

Bold values represent p < 0.05.

Fisher's exact tests.

Other statins include cerivastatin, fluvastatin and pitavastatin.

§

The statin dose was counted as 0 for participants taking a non-statin or no statin.

SAMS: Statin-associated muscle symptoms.

The results for the logistic regression models for the primary outcome of SAMS resolution are presented in Table3. CoQ10 was not significantly associated with the resolution of SAMS in any model. The only variable that was significantly associated with the resolution of SAMS was when a participant took lovastatin compared with atorvastatin. The odds of SAMS resolving were higher with lovastatin than atorvastatin (OR: 4.50 [95% CI: 1.77–11.43]; p=0.011). However, those results should be interpreted with caution because of the extremely small sample size (only two CoQ10 users were taking lovastatin) and multiple comparisons. The results for the secondary outcome of statin continuation despite a history of SAMS are presented in Table4. Of the 511 total participants that had experienced SAMS in the past, only 171 (33%) were still taking a statin currently. CoQ10 use was not significantly associated with the continuation of statin therapy in any model, nor were any of the other variables.

Table 3.. Logistic regression results for association of coenzyme Q10 with the resolution of statin-associated muscle symptoms.

VariablesOdds ratio (95% CI)p-value
Model 1 (unadjusted)
Coenzyme Q10 use0.75 (0.41–1.38)0.357
Model 2 (adjusted)
Coenzyme Q10 use0.84 (0.45–1.55)0.568
Hypertension1.29 (0.87–1.90)0.210
Obesity1.35 (0.81–2.24)0.257
Smoking1.13 (0.75–1.71)0.555
Lovastatin vs atorvastatin4.50 (1.77–11.43)0.011
Pravastatin vs atorvastatin1.42 (0.69–2.94)0.670
Rosuvastatin vs atorvastatin1.42 (0.80–2.53)0.602
Simvastatin vs atorvastatin1.35 (0.82–2.22)0.407
Other statin vs atorvastatin1.52 (0.44–5.26)0.897
Family history of heart disease0.83 (0.56–1.22)0.343
Model 3§ (adjusted)
Coenzyme Q10 use0.82 (0.45–1.51)0.522
Smoking1.09 (0.73–1.63)0.670
Obesity1.39 (0.84–2.29)0.203
Family history of muscle disease1.51 (0.64–3.59)0.350

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Bold p-values indicate p < 0.05.

Adjusted for the five variables that were statistically significant in the original study for an association with SAMS [15].

Other statins include cerivastatin, fluvastatin, and pitavastatin.

§

Adjusted for the three variables that were significantly different between Coenzyme Q10 users and non-users in Table1.

SAMS: Statin-associated muscle symptoms.

Table 4.. Logistic regression results for association of coenzyme Q10 with the continuation of statin therapy despite a history of statin-associated muscle symptoms.

VariablesOdds ratio (95% CI)p-value
Model 1 (unadjusted)
Coenzyme Q10 use1.05 (0.60–1.82)0.868
Model 2 (adjusted)
Coenzyme Q10 use1.07 (0.61–1.89)0.804
Hypertension0.81 (0.55–1.18)0.265
Obesity1.31 (0.81–2.11)0.277
Smoking0.93 (0.63–1.37)0.696
Lovastatin vs atorvastatin0.80 (0.30–2.15)0.851
Pravastatin vs atorvastatin0.85 (0.41–1.77)0.952
Rosuvastatin vs atorvastatin1.18 (0.68–2.05)0.232
Simvastatin vs atorvastatin0.89 (0.55–1.44)0.920
Other statin vs atorvastatin0.60 (0.16–2.28)0.512
Family history of heart disease0.71 (0.48–1.03)0.068
Model 3§ (adjusted)
Coenzyme Q10 use1.09 (0.62–1.92)0.761
Smoking1.10 (0.75–1.61)0.633
Obesity0.81 (0.51–1.30)0.383
Family history of muscle disease0.64 (0.28–1.46)0.287

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Bold p-values indicate p < 0.05.

Adjusted for the five variables that were statistically significant in the original study for an association with SAMS [15].

Other statins include cerivastatin, fluvastatin and pitavastatin.

§

Adjusted for the three variables that were significantly different between Coenzyme Q10 users and non-users in Table1.

SAMS: Statin-associated muscle symptoms.

Discussion

In this observational, multicenter study, CoQ10 use was not significantly associated with the resolution of SAMS or the continuation of statin therapy despite a past history of SAMS. This study adds to the current body of literature because it is one of the largest studies to date. These findings are important because even though the current AHA/ACC guideline recommends against the use of CoQ10 for the treatment of SAMS [2], CoQ10 is widely available over the counter and still used by many patients. Several randomized, controlled trials (RCTs) have tested the effectiveness of CoQ10 in treating SAMS [17–24], but the interpretation is unclear because some of the CoQ10 RCTs found significant benefit but others did not. Four meta-analyses of those individual RCTs have attempted to yield clarity on this issue [10–13]. One of those meta-analyses showed a significant benefit of CoQ10 for treating SAMS [11], whereas the other three did not [10,12,13]. These meta-analyses all used different methods, but the authors believe that the most likely explanation for the differences in the results of these meta-analyses are differences in power. The meta-analysis that found significant benefit for CoQ10 had the largest sample size (total n=575) [11]. The other three meta-analyses all trended toward benefit for CoQ10, but they failed to find a significant association with much smaller sample sizes (total n=253, n=220 and n=321) [10,12,13]. The findings of the present study could contribute to future meta-analyses.

Several possible explanations for the lack of benefit associated with CoQ10 for the treatment of SAMS, in this study and in previous studies, are worth noting. First, even though the sample size of this study is larger or comparable to previous studies, it still had low power to detect small beneficial effects of CoQ10 because only 64 participants reported using CoQ10. The authors estimated that SAMS would need to resolve in 2.5 times more CoQ10 users than non-users to be detectable in this study, which is an extremely large effect size. However, it does not appear that the lack of association in this study is due to low power, as none of the ORs for CoQ10 were >1 for an association with resolution of SAMS. Second, true SAMS is extremely difficult to diagnose. In order to overcome that difficulty, some previous studies restricted enrollment to only patients that passed a run-in period. For example, Taylor et al. utilized a randomized, double-blind and crossover run-in period prior to their RCT of CoQ10 for SAMS [23]. Only participants that experienced muscle pain on simvastatin, but not on placebo, were entered into the CoQ10 RCT. Only 36% of the participants passed the run-in period, demonstrating that most patients may not have true SAMS but only a nocebo effect. In the present study, the relationship between statin use and muscle symptoms must have been clear to the participants and their physician, but the study did not have a placebo run-in period like the aforementioned study by Taylor et al. However, a disadvantage of a placebo run-in period would be that it would only include participants that had an acute onset of SAMS; it would exclude participants with a more delayed onset of SAMS.

A third possible explanation for the lack of effectiveness of CoQ10 in this study and previous studies is that the dose of CoQ10 was too low. The adult human body contains approximately 2 g of CoQ10, of which 500mg must be replaced daily, either through diet or endogenous production [25]. All of the previous RCTs used doses less than 500mg per day [17–24], except for the RCT by Taylor et al., which used 600mg per day. Moreover, it is postulated that the supplement should be taken a number of weeks before starting a statin, so that the muscle stores are replete. However, the aforementioned Taylor et al. study utilized a 2-week loading period, in which the participants were treated with either placebo or CoQ10 for 2 weeks prior to the start of statin use, but they still did not detect a significant benefit with CoQ10. Some of the previous RCTs also measured plasma levels of CoQ10 [17,19,20,22–24]. In the present study, the participants did not report their dose or duration of CoQ10 use, only whether or not they were taking it. Therefore, the authors were unable to assess whether or not the participants were taking a sufficient replacement dose of CoQ10. On the other hand, the dose of CoQ10 may not make a difference in SAMS. Studies in rats showed that although dietary CoQ10 increases serum levels, it does not increase the levels of CoQ10 in muscle [26].

A fourth potential explanation for a lack of benefit is that CoQ10 supplementation may only be effective in participants with an established CoQ10 deficiency [27]. SAMS has multiple suspected etiologies, including pre-existing underlying neuromuscular disorders, auto-immune reactions and vitamin D deficiency [28]. However, this study did not measure CoQ10 serum levels in participants upon enrollment. Thus, the authors cannot confirm that all participants had a CoQ10 deficiency secondary to statin therapy, nor can they confirm that CoQ10 plasma levels significantly increased with CoQ10 use. Finally, the lack of association in this study could simply mean that CoQ10 is not effective for the treatment of SAMS. Some point out that a direct causal link between CoQ10 deficiency and SAMS has still not been well established [29–31].

This study has several limitations in addition to those described above. The major limitation is that it was not an RCT, which is the gold standard for evaluating effectiveness of an intervention. As with any observational study, cause-and-effect could not be determined – for example, did the patients stop taking the CoQ10 because it either did or did not work? The duration of CoQ10 therapy was unknown, and there was no information on whether CoQ10 had been used prophylactically or only for treatment. The bioavailability of CoQ10 is dependent on the formulation [32], but the formulation was unknown as well. The outcome of this study is subjective and reported by the participants, and thus it is subject to recall bias. Another limitation is that the survey did not collect either the participants' dietary intake or physical activity data [33]. The survey also did not collect the participants' BMI. However, the questionnaire did include whether or not the participants had obesity, and the authors adjusted both models 2 and 3 for obesity as a covariate. The authors do not expect that using obesity instead of BMI would have impacted the results in a major way because obesity was not statistically significant in either model, and the association of CoQ10 was similar regardless of which covariates were included in the models. Finally, the sample consisted entirely of Caucasian participants, and thus it is unknown whether these findings apply to other racial/ethnic groups.

Conclusion & future directions

In this multicenter, observational study of 511 Caucasians with a history of SAMS, the addition of CoQ10 for 64 participants was not significantly associated with either the resolution of SAMS or the continuation of statin therapy. The lack of association was consistent in multiple different logistic regression models, regardless of the covariates used (e.g., risk factors for SAMS or baseline differences among CoQ10 users and non-users). There are several potential explanations for this lack of CoQ10 benefit (e.g., insufficient dose, duration or formulation of CoQ10). This supports the current AHA/ACC recommendation against the use of CoQ10 in the treatment of SAMS.

Based on these and others' findings, and for several other reasons, the authors do not believe that future research should continue to investigate CoQ10 for the treatment of SAMS. The ideal clinical trial that is needed to definitively determine the effectiveness of CoQ10 for the treatment of SAMS would have an excessive number of design requirements, such as a run-in period to distinguish participants with true SAMS versus those with only nocebo effect; screening for enrollment of only participants with known CoQ10 deficiency; a loading period to ensure sufficient CoQ10 levels prior to the start of the statin; treatment with high doses of CoQ10 (at least 500mg per day); and treatment with a CoQ10 formulation with maximal bioavailability. Finally, it would need to be a randomized, placebo-controlled trial with sufficient power to detect only small benefit (and thus a very large sample size). Given the high cost of such a clinical trial, the expected small benefit of CoQ10 (based on the results of the meta-analyses) and the availability of new, alternative agents (i.e., PCSK9 inhibitors), such a trial for CoQ10 is not necessary. Future research should focus more on the prevention instead of the treatment of SAMS. For example, there are now clinical practice guidelines on the use of patients' genetics to decrease the risk of SAMS [34].

Summary points.

  • Coenzyme Q10 (CoQ10) is an attractive option for treating statin-associated muscle symptoms (SAMS), since it is widely available over the counter, it is well tolerated and it would allow for continued statin-based treatments with cardioprotective effects.

  • However, the effectiveness of CoQ10 for the treatment of SAMS is currently unclear.

  • Therefore, the primary purpose of this study was to determine whether CoQ10 use is associated with the resolution of SAMS.

  • This was a retrospective analysis of a large, multicenter survey study of SAMS (total n=511; n=64 CoQ10 users).

  • CoQ10 use was not significantly associated with the resolution of SAMS in any logistic regression model (unadjusted or adjusted for clinical risk factors or differences).

  • Potential explanations for this lack of benefit of CoQ10 for SAMS include a very small (and therefore difficult to detect) benefit of CoQ10; the difficulty in identifying true SAMS versus non-specific muscle symptoms; very high doses of CoQ10 may be required; and/or the selective benefit of CoQ10 (i.e., CoQ10 may only be effective in participants with an established CoQ10 deficiency).

Footnotes

Author contributions

All authors meet all of the following four criteria: substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

This work was supported by grants from the National Institutes of Health (R01 HL085800 to GD Vladutiu; R21 AR055704 to PJ Isackson; and K08 HL146990 and Loan Repayment Program L30 HL110279 to JA Luzum); the John R. Oishei Foundation; and an Interdisciplinary Research and Creative Activities Award from the University at Buffalo Office of the Vice President for Research (to GD Vladutiu). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Coenzyme Q10 supplementation for the treatment of statin-associated muscle symptoms (2024)
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