Trial reportJournal of the American College of Cardiology2013

Simvastatin impairs exercise training adaptations.

Catherine R Mikus, Leryn J Boyle, Sarah J Borengasser, Douglas J Oberlin, Scott P Naples, Justin Fletcher, Grace M Meers, Meghan Ruebel, M Harold Laughlin, Kevin C Dellsperger and 2 more

4 registry-linked trialsAbstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American College of Cardiology, 2013. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It reports registered trial NCT01700530. Cited by 97 papers, 1 of them a synthesis that pooled it.

1number the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
31.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Adverse events & safetycomparator not stated · ascvd, dyslipidemiafeeds 2 cells of the map
increase 10.0p < 0.05
Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Diet, exercise & lifestyle×adverse events & safety

No readable resultOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Statins×adverse events & safety

No readable resultOpen on the map →What to test next →

11 readable studies in this cell: 3 favour the treatment, 7 find no difference, 1 favour the comparator.

Belief with this paper
0.16contested · 1 family supports, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ 13.79.40 to 18.0
NCT01294683977 enrolled · 2011
Δ -1.03-7.30 to 5.25
NCT00728988499 enrolled · 2008
Δ 1.00-7.30 to 9.30
NCT01678820299 enrolled · 2012
Δ -0.40-10.2 to 9.30

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01700530 nacompleted

Exercise, Statins, and the Metabolic Syndrome

Ran2007Enrolled121Registered outcomes2Posted comparisons1ConditionsMetabolic Syndrome, Obese, SedentaryArmsExercise only, Statin, Statins + Exercise
Open the trial in the graph
NCT06841536 nacompletedstarted 2025, after this paper: background citation

Combined Effects of Statins and Exercise on Physiological Health Markers and Quality of Life in Patients With Dyslipidaemia

Ran2025Enrolled120Registered outcomes61Posted comparisons0ConditionsDyslipidemiasArmsAtorvastatin 80mg, Exercise
Open the trial in the graph
NCT07401017 nanot yet recruitingstarted 2026, after this paper: background citation

The Effects of Rosuvastatin on Physiological Adaptation and Safety During Regular Long-Distance Running Training: A Randomized Controlled Trial

Ran2026Enrolled40Registered outcomes7Posted comparisons0ConditionsDyslipidemia, Endurance Training, Long-Distance Running, Statin-Associated Muscle SymptomsArmsRosuvastatin
Open the trial in the graph
NCT07563452 narecruitingnot on this mapstarted 2026, after this paper: background citation

Investigating the Role of Mechanical Muscle Loading in the Context of Preventive Exercise for Statin Users - a Pilot Study

TypeinterventionalSponsorRaffaele MazzolariRan2026 to 2027Enrolled40ConditionsStatin Adverse ReactionArmsDose-Escalation Exercise Protocol
5 · Its place in the literature

Who cites it

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.

  1. Statins, mood, sleep, and physical function: a systematic review.European journal of clinical pharmacology · 2014
    Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy.Translational research : the journal of laboratory and clinical medicine · 2015
    Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

37 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Catherine R MikusDivision of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
Leryn J Boyle
Sarah J Borengasser
Douglas J Oberlin
Scott P Naples
Justin Fletcher
Grace M Meers
Meghan Ruebel
M Harold Laughlin
Kevin C Dellsperger
Paul J Fadel
John P Thyfault
University of Missouri · USDuke Medical Center · USDuke University · USUniversity of Arkansas for Medical Sciences · US

Funding

Exercise &Health: Integration from Molecule to PatientT32AR048523 · UNIVERSITY OF MISSOURI-COLUMBIA · 2003 to 2005
$695k
NIAMS NIH HHS T32 AR048523
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectivesThis study sought to determine if simvastatin impairs exercise training adaptations.

backgroundStatins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training.

methodsThis study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity).

resultsThirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction).

conclusionsSimvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530).

Indexed as

Adaptation, PhysiologicalAdultAnticholesteremic AgentsCardiovascular DiseasesCitrate (si)-SynthaseCombined Modality TherapyExerciseExercise TherapyFemaleHumansLipoproteinsMaleMetabolic SyndromeMiddle AgedMitochondria, MuscleOverweightAnticholesteremic AgentsCitrate (si)-SynthaseLipoproteinsSimvastatinaerobic fitnessBMIbody mass indexLDL-Clow-density lipoprotein cholesterolmetabolic syndromeobesitypeak oxygen consumptionskeletal muscle mitochondriastatinVo(2)peak

Identifiers

PMID23583255
PMCPMC3745788
OpenAlexW1974187375

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.