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Cited by 13Lipoproteins and Cardiovascular HealthAntioxidant Activity and Oxidative StressTrace Elements in Health

The Hypolipidemic and Pleiotropic Effects of Rosuvastatin Are Not Enhanced by Its Association with Zinc and Selenium Supplementation in Coronary Artery Disease Patients: A Double Blind Randomized Controlled Study

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Sena-Evangelista, Karine Cavalcanti Maurício, Pedrosa, Lucia Fatima Campos, Paiva, Maria Sanali Moura Oliveira, Dias, Paula Cristina Silveira, Ferreira, Diana Quitéria Cabral, Cozzolino, Sílvia Maria Franciscato, Faulin, Tanize Espírito Santo, Abdalla, Dulcinéia Saes Parra·2015·PLOS ONE
DOI 10.1371/journal.pone.0119830PMC PMC4365008
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Abstract

OBJECTIVE: Statins treatment may modify the levels of zinc and selenium, minerals that can improve vascular function and reduce oxidative damage and inflammation in atherosclerotic patients. This study aimed to evaluate the effects of rosuvastatin, alone or associated with zinc and selenium supplementation, on lipid profile, antioxidant enzymes and mineral status in coronary artery disease patients. MATERIAL AND METHODS: A double-blind randomized clinical trial was performed in which patients (n = 76) were treated with 10 mg rosuvastatin over 4 months associated or not with zinc (30 mg/d) and selenium (150 μg/d) supplementation. The following parameters were analyzed before and after the intervention: anthropometric measurements, lipid profile, high sensitivity C-reactive protein (hs-CRP), electronegative low density lipoprotein (LDL(-)) concentrations, activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), zinc and selenium concentrations in blood plasma and erythocytes. Significance was determined using an α of 5% (two-tailed). RESULTS: We found that rosuvastatin therapy was efficient in reducing total cholesterol, LDL-cholesterol, non-HDL cholesterol, triglycerides, and hs-CRP independently of mineral supplementation. Neither treatment was associated with significant changes in LDL(-). Similarly, the antioxidant enzymes GPx and SOD activity were unchanged by treatments. Neither treatment was associated with significant differences in concentrations of zinc or selenium in blood plasma and erythocytes of studied groups. CONCLUSION: Rosuvastatin treatment did not affect zinc and selenium levels in coronary artery disease patients. The zinc and selenium supplementation at doses used in this study did not change lipid profile or SOD and GPx activity in patients receiving rosuvastatin. Further studies should be focused on testing alternative doses and supplements in different populations to contribute for a consensus on the ideal choice of antioxidants to be used as possible complementary therapies in atherosclerotic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01547377.

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Crossref · 10.1371/journal.pone.0119830

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  • All selected trials investigate the impact of daily oral CoQ10 supplementation on muscle pain under statin therapy.

    “All selected trials investigate the impact of a daily oral CoQ10 supplementation on muscle pain under statin therapy.(33,34,39–43)”

    From Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis (2025) · cites this paper as [42]

    The Materials and Methods (Study Procedures; page not available) describe rosuvastatin with daily zinc and selenium supplementation or placebo, not CoQ10. The Primary and Secondary Endpoints section identifies LDL cholesterol as the primary endpoint and does not list muscle pain as an endpoint. This trial therefore does not fit the cited description. (LLM, conf=0.90)

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  • Two trials do not report medication intake.

    “While one trial did not exclude respective patients but reports the intake of pain medication as part of the study characteristics,(43) two other trials do not report medication intake.(33,42)”

    From Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis (2025) · cites this paper as [42]

    The Results (Subjects, Table 1; page not provided) report medication use before randomization, including statins, antiplatelets, and antihypertensives. Thus this trial does report medication intake, although the table does not separately list pain medication. The other trial cited in the sentence cannot be assessed from this source. (LLM, conf=0.88)

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  • One study investigated CoQ10 and selenium in double placebo-controlled subgroups but reports combined results, not CoQ10 effects solely, leading to high overall risk of bias.

    “The other study investigated the effects of both a CoQ10 and a selenium supplementation in double placebo-controlled subgroups but reports the results of the subgroups in a combined manner, not reporting the effects of the CoQ10 supplementation solely. Consequently, the overall risk of bias in this study is considered high.(42)”

    From Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis (2025) · cites this paper as [42]

    The Materials and Methods (Study Procedures) describe a double-blind comparison of combined zinc and selenium supplementation against a placebo, both alongside rosuvastatin—not CoQ10 and selenium supplementation in separate placebo-controlled subgroups. The Study Population section likewise describes two allocated groups. The cited paper therefore contradicts the premise used to explain the citing authors’ high-risk-of-bias judgment. (LLM, conf=0.90)

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  • Selection of reported results causes a moderate to high risk of bias in two studies.

    “The domain “selection of reported results” causes a moderate to high risk of bias in two studies.(41,42)”

    From Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis (2025) · cites this paper as [42]

    The Ethics Statement (page unavailable) says the trial was registered after the authors obtained all results, a fact relevant to assessing selection of reported results. The paper does not itself assign a moderate-to-high risk-of-bias rating or establish that two studies received that rating. (LLM, conf=0.76)

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  • Some concerns result from the randomisation process in two studies because allocation is claimed to be random but is not described in detail.

    “Some concerns result from the randomisation process in two studies, as the allocation of participants is claimed to be random but is not described in detail.(33,42)”

    From Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis (2025) · cites this paper as [42]

    The Materials and Methods (Study Population) say that 93 participants were randomly allocated. Study Procedures describe coded supplement and placebo bottles, a 50/50 ratio in batches, and random assignment of bottles, but do not specify how the random assignment was generated. Thus the concern about an unspecified randomisation method is supported, although the paper does describe other allocation procedures in detail. (LLM, conf=0.83)

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Cites

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Cited by

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Authors
Sena-Evangelista, K. C. M., Pedrosa, L. F. C., Paiva, M. S. M. O., Dias, P. C. S., Ferreira, D. Q. C., Cozzolino, S. M. F., Faulin, T. E. S., & Abdalla, D. S. P.
Affiliations
  • Universidade Federal do Rio Grande do Norte (BR)
  • Universidade de São Paulo (BR)
Corresponding author
Abdalla, Dulcinéia Saes Parra
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-03-18
Volume
10
Issue
3
Pages
e0119830
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0119830
PMC
PMC4365008
OpenAlex
W2035805509
Cited by
13
References
2
Citations by year
2025: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2017: 2
FWCI
0.67
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Varian Medical Systems
  • Governo Brasil
  • Fundação de Apoio à Pesquisa do Rio Grande do Norte (981-199697778)
  • Universidade Federal do Rio Grande do Norte
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
rosuvastatin, zinc supplementation, selenium supplementation, coronary artery disease, lipid profile, antioxidant enzymes, glutathione peroxidase, superoxide dismutase, C-reactive protein, LDL cholesterol, oxidative stress, mineral status, statins, atherosclerosis
MeSH terms
Rosuvastatin Calcium, Hypolipidemic Agents, C-Reactive Protein, Coronary Artery Disease, Female, Glutathione Peroxidase, Humans, Lipids, Lipoproteins, LDL, Male, Selenium, Superoxide Dismutase, Zinc, Treatment Outcome, Statistics, Nonparametric, Dietary Supplements

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