Simvastatin

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"}

experimental_model

Randomized double-blind placebo-controlled trial with muscle biopsies

exposure

Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks

limitations

Different statin/dose regimens. Respiratory-enzyme comparison selected six simvastatin participants with marked CoQ decline and matched participants; not an unbiased whole-arm estimate.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

48 hypercholesterolemic adults in three groups

plain_language

Some regimens lowered the muscle pool, but the finding did not apply equally to every statin arm.

primary_references

[coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

tissue_or_cell_type

Muscle CoQ and respiratory enzymes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial with muscle biopsies · source_derived_draft · unverified_draft

### coq10-statin-muscle-low Muscle CoQ fell from 39.7 to 26.4 nmol/g with simvastatin 80 mg/day; it did not fall with atorvastatin 40 mg/day or placebo. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some regimens lowered the muscle pool, but the finding did not apply equally to every statin arm. organism: 48 hypercholesterolemic adults in three groups tissue_or_cell_type: Muscle CoQ and respiratory enzymes experimental_model: Randomized double-blind placebo-controlled trial with muscle biopsies limitations: Different statin/dose regimens. Respiratory-enzyme comparison selected six simvastatin participants with marked CoQ decline and matched participants; not an unbiased whole-arm estimate. exposure: Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"} [coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

evidence_span

{"source_cache": "artifacts/coq10-research/16872244.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "65abd11b5f58ce1125f554d52ed5203575d7a3ba0d20b789abce16148f3b5e27", "start_char": 0, "end_char": 2245, "text_sha256": "65abd11b5f58ce1125f554d52ed5203575d7a3ba0d20b789abce16148f3b5e27"}

experimental_model

Randomized three-arm parallel study

exposure

Simvastatin 40 mg/day, ezetimibe 10 mg/day or both for 14 days

limitations

Plasma measurements and correlation; neither tissue CoQ nor mitochondrial dysfunction was demonstrated.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

72 healthy men

plain_language

The blood concentration also depends on the particles carrying CoQ.

primary_references

[coq10-p16872244] Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial. (2006). https://pubmed.ncbi.nlm.nih.gov/16872244/ DOI: 10.2165/00002018-200629080-00007

tissue_or_cell_type

Plasma CoQ and lipoprotein concentrations

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 931–942

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized three-arm parallel study · source_derived_draft · unverified_draft

### coq10-statin-plasma-carriers Simvastatin, alone or with ezetimibe, lowered plasma CoQ; CoQ change correlated with LDL-cholesterol change and the CoQ-to-LDL ratio increased. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood concentration also depends on the particles carrying CoQ. organism: 72 healthy men tissue_or_cell_type: Plasma CoQ and lipoprotein concentrations experimental_model: Randomized three-arm parallel study limitations: Plasma measurements and correlation; neither tissue CoQ nor mitochondrial dysfunction was demonstrated. exposure: Simvastatin 40 mg/day, ezetimibe 10 mg/day or both for 14 days evidence_span: {"source_cache": "artifacts/coq10-research/16872244.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "65abd11b5f58ce1125f554d52ed5203575d7a3ba0d20b789abce16148f3b5e27", "start_char": 0, "end_char": 2245, "text_sha256": "65abd11b5f58ce1125f554d52ed5203575d7a3ba0d20b789abce16148f3b5e27"} [coq10-p16872244] Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial. (2006). https://pubmed.ncbi.nlm.nih.gov/16872244/ DOI: 10.2165/00002018-200629080-00007

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"}

experimental_model

Randomized double-blind placebo-controlled trial with muscle biopsies

exposure

Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks

limitations

Six selected simvastatin participants were compared with matched participants from other arms. Selection and mitochondrial-content changes prevent assigning the entire effect specifically to CoQ depletion.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

48 hypercholesterolemic adults in three groups

plain_language

Both respiratory capacity and a mitochondrial-content marker changed in a selected subgroup.

primary_references

[coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

tissue_or_cell_type

Muscle CoQ and respiratory enzymes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 970–981

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial with muscle biopsies · source_derived_draft · unverified_draft

### coq10-statin-respiratory-subset Respiratory-chain enzyme and citrate-synthase activities were lower in the selected simvastatin subgroup with marked muscle CoQ decline. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both respiratory capacity and a mitochondrial-content marker changed in a selected subgroup. organism: 48 hypercholesterolemic adults in three groups tissue_or_cell_type: Muscle CoQ and respiratory enzymes experimental_model: Randomized double-blind placebo-controlled trial with muscle biopsies limitations: Six selected simvastatin participants were compared with matched participants from other arms. Selection and mitochondrial-content changes prevent assigning the entire effect specifically to CoQ depletion. exposure: Simvastatin 80 mg/day, atorvastatin 40 mg/day or placebo for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/16003294.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b", "start_char": 0, "end_char": 1774, "text_sha256": "6293a60171af6eb5cc8dc58449792c024ee282cdbcb80f777dc9156f4c44250b"} [coq10-p16003294] High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

evidence_span

{"source_cache": "artifacts/coq10-research/7828383.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197", "start_char": 0, "end_char": 800, "text_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197"}

experimental_model

Short-term treatment with serum and muscle sampling

exposure

Four weeks of simvastatin

limitations

Small short-term study; serum and muscle moved differently. No participants developed myopathy; this does not exclude other regimens or vulnerable patients.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Humans with hypercholesterolemia

plain_language

A falling blood result did not mean falling muscle supply in this study.

primary_references

[coq10-p7828383] Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7828383/ DOI: 10.1016/0009-9236(95)90266-x

tissue_or_cell_type

Serum versus skeletal-muscle CoQ

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 918–929

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Short-term treatment with serum and muscle sampling · source_derived_draft · unverified_draft

### coq10-statin-serum-muscle After four weeks, serum ubiquinone decreased while muscle ubiquinone increased; no participant developed myopathy. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A falling blood result did not mean falling muscle supply in this study. organism: Humans with hypercholesterolemia tissue_or_cell_type: Serum versus skeletal-muscle CoQ experimental_model: Short-term treatment with serum and muscle sampling limitations: Small short-term study; serum and muscle moved differently. No participants developed myopathy; this does not exclude other regimens or vulnerable patients. exposure: Four weeks of simvastatin evidence_span: {"source_cache": "artifacts/coq10-research/7828383.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197", "start_char": 0, "end_char": 800, "text_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197"} [coq10-p7828383] Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7828383/ DOI: 10.1016/0009-9236(95)90266-x

evidence_span

{"source_cache": "artifacts/coq10-research/7828383.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197", "start_char": 0, "end_char": 800, "text_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197"}

experimental_model

Short-term treatment with serum and muscle sampling

exposure

Four weeks of simvastatin

limitations

Established biochemical background described in this primary report; enzyme target engagement was not the independent endpoint of this serum/muscle study.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Humans with hypercholesterolemia

plain_language

A cholesterol-lowering drug acts upstream of more than cholesterol.

primary_references

[coq10-p7828383] Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7828383/ DOI: 10.1016/0009-9236(95)90266-x

tissue_or_cell_type

Serum versus skeletal-muscle CoQ

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 905–916

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Short-term treatment with serum and muscle sampling · source_derived_draft · unverified_draft

### coq10-statin-target Simvastatin inhibits HMG-CoA reductase, an upstream enzyme in the mevalonate pathway shared by sterol and CoQ precursor production. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cholesterol-lowering drug acts upstream of more than cholesterol. organism: Humans with hypercholesterolemia tissue_or_cell_type: Serum versus skeletal-muscle CoQ experimental_model: Short-term treatment with serum and muscle sampling limitations: Established biochemical background described in this primary report; enzyme target engagement was not the independent endpoint of this serum/muscle study. exposure: Four weeks of simvastatin evidence_span: {"source_cache": "artifacts/coq10-research/7828383.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197", "start_char": 0, "end_char": 800, "text_sha256": "e6aac0f5f784ab8a43755c6c878ea010b8673acc19bfa41f7a1272880c745197"} [coq10-p7828383] Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7828383/ DOI: 10.1016/0009-9236(95)90266-x

duration

3 days of gemfibrozil, 12 hours of sampling

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

10 healthy volunteers, double-blind randomised crossover

exposure

Gemfibrozil 600 mg twice daily for 3 days, then a single 40 mg simvastatin dose

limitations

Gemfibrozil did not inhibit CYP3A4 in human liver microsomes, so the interaction is not a CYP3A4 effect; the authors attribute it to inhibition of non-CYP3A4 metabolism of simvastatin acid.

organism

10 healthy volunteers, double-blind randomised crossover

plain_language

Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.

primary_references

Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507

route

Oral

tissue

Plasma simvastatin lactone and active simvastatin acid

Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 24–33

Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## gemfibrozil-raises-simvastatin-acid-exposure Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent. Model/species: 10 healthy volunteers, double-blind randomised crossover Tissue/system: Plasma simvastatin lactone and active simvastatin acid Exposure: Gemfibrozil 600 mg twice daily for 3 days, then a single 40 mg simvastatin dose Route: Oral Duration: 3 days of gemfibrozil, 12 hours of sampling Limits: Gemfibrozil did not inhibit CYP3A4 in human liver microsomes, so the interaction is not a CYP3A4 effect; the authors attribute it to inhibition of non-CYP3A4 metabolism of simvastatin acid. Primary reference: Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Mean follow-up 6.7 years

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

12,064 men and women aged 18-80 with a history of myocardial infarction

exposure

80 mg versus 20 mg simvastatin daily, randomised double-blind

limitations

Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer.

organism

12,064 men and women aged 18-80 with a history of myocardial infarction

plain_language

Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.

primary_references

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8

route

Oral

tissue

Myopathy as an adverse outcome

Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 13–22

Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## simvastatin-dose-raises-myopathy Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily. Model/species: 12,064 men and women aged 18-80 with a history of myocardial infarction Tissue/system: Myopathy as an adverse outcome Exposure: 80 mg versus 20 mg simvastatin daily, randomised double-blind Route: Oral Duration: Mean follow-up 6.7 years Limits: Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer. Primary reference: Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

3 days

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

10 healthy volunteers, with the myopathy association drawn from prior case reports

exposure

Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent

limitations

This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers.

organism

10 healthy volunteers, with the myopathy association drawn from prior case reports

plain_language

The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.

primary_references

Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507

route

Oral

tissue

Plasma simvastatin acid concentration and muscle injury risk

Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 35–44

Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## simvastatin-exposure-raises-myopathy The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin. Model/species: 10 healthy volunteers, with the myopathy association drawn from prior case reports Tissue/system: Plasma simvastatin acid concentration and muscle injury risk Exposure: Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent Route: Oral Duration: 3 days Limits: This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers. Primary reference: Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

8 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo

exposure

Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks

limitations

Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g.

organism

48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo

plain_language

Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.

primary_references

High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006

route

Oral

tissue

Skeletal muscle ubiquinone measured in biopsy specimens

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 177–186

Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## atorvastatin-muscle-ubiquinone-null Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms. Model/species: 48 patients with hypercholesterolaemia randomised to simvastatin 80 mg/d, atorvastatin 40 mg/d or placebo Tissue/system: Skeletal muscle ubiquinone measured in biopsy specimens Exposure: Simvastatin 80 mg/d or atorvastatin 40 mg/d for 8 weeks Route: Oral Duration: 8 weeks Limits: Endogenous cholesterol synthesis fell by 66 percent in both statin groups, so the muscle result is not explained by weaker target engagement; the simvastatin fall was from 39.7 to 26.4 nmol/g. Primary reference: High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. (2005). https://pubmed.ncbi.nlm.nih.gov/16003294/ DOI: 10.1016/j.clpt.2005.03.006 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Murine C2C12 myoblasts

exposure

Atorvastatin at IC50, alongside simvastatin and methyl-beta-cyclodextrin

limitations

An IC50 exposure in a proliferating myoblast line is not a therapeutic muscle concentration in a person.

organism

Murine C2C12 myoblasts

plain_language

Atorvastatin at its half-maximal inhibitory concentration reduced the viability of proliferating murine C2C12 myoblasts.

primary_references

Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807

route

In vitro

tissue

Muscle cell viability and regeneration in vitro

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 111–120

Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## atorvastatin-reduces-myoblast-viability Atorvastatin at its half-maximal inhibitory concentration reduced the viability of proliferating murine C2C12 myoblasts. Model/species: Murine C2C12 myoblasts Tissue/system: Muscle cell viability and regeneration in vitro Exposure: Atorvastatin at IC50, alongside simvastatin and methyl-beta-cyclodextrin Route: In vitro Duration: Not stated here Limits: An IC50 exposure in a proliferating myoblast line is not a therapeutic muscle concentration in a person. Primary reference: Geranylgeraniol Prevents Statin-Dependent Myotoxicity in C2C12 Muscle Cells through RAP1 GTPase Prenylation and Cytoskeletal Stabilization. (2018). https://pubmed.ncbi.nlm.nih.gov/29951166/ DOI: 10.1155/2018/6463807 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Trial duration, not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial

exposure

Simvastatin 80 mg daily, replication at simvastatin 40 mg daily

limitations

The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects.

organism

85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial

plain_language

A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.

primary_references

SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936

route

Oral

tissue

Hepatic statin uptake and skeletal muscle injury

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 133–142

Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## slco1b1-variant-and-statin-myopathy A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1. Model/species: 85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial Tissue/system: Hepatic statin uptake and skeletal muscle injury Exposure: Simvastatin 80 mg daily, replication at simvastatin 40 mg daily Route: Oral Duration: Trial duration, not stated here Limits: The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects. Primary reference: SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

{"source_cache": "artifacts/coq10-research/25545331.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837", "start_char": 0, "end_char": 1976, "text_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837"}

experimental_model

Randomized double-blind trial after blinded symptom confirmation

exposure

600 mg/day ubiquinol with simvastatin 20 mg/day for eight weeks

limitations

Small confirmed-myalgia sample; null outcome is not proof that every other regimen is ineffective.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

41 subjects with confirmed simvastatin myalgia

plain_language

A more strictly selected trial did not reproduce the pain benefit.

primary_references

[coq10-p25545331] A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. (2015). https://pubmed.ncbi.nlm.nih.gov/25545331/ DOI: 10.1016/j.atherosclerosis.2014.12.016

tissue_or_cell_type

Pain, muscle performance and serum CoQ

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1165–1176

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial after blinded symptom confirmation · source_derived_draft · unverified_draft

### coq10-statin-pain-null Ubiquinol did not reduce pain severity or interference versus placebo in confirmed simvastatin myalgia. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A more strictly selected trial did not reproduce the pain benefit. organism: 41 subjects with confirmed simvastatin myalgia tissue_or_cell_type: Pain, muscle performance and serum CoQ experimental_model: Randomized double-blind trial after blinded symptom confirmation limitations: Small confirmed-myalgia sample; null outcome is not proof that every other regimen is ineffective. exposure: 600 mg/day ubiquinol with simvastatin 20 mg/day for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/25545331.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837", "start_char": 0, "end_char": 1976, "text_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837"} [coq10-p25545331] A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. (2015). https://pubmed.ncbi.nlm.nih.gov/25545331/ DOI: 10.1016/j.atherosclerosis.2014.12.016

evidence_span

{"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"}

experimental_model

Open-label randomized parallel pharmacokinetic study

exposure

Single-dose and seven-day repeated treatment; berberine chloride alone or combined

limitations

Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Sixty healthy Chinese participants across five groups

plain_language

The measured result limits a blanket claim that every relevant drug concentration must rise.

primary_references

[berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487

tissue_or_cell_type

Simvastatin and fenofibrate exposure

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 935–946

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open-label randomized parallel pharmacokinetic study · source_derived_draft · unverified_draft

### berberine-clinical-statin-null No clinically obvious pharmacokinetic interaction with simvastatin was detected in the tested berberine-chloride combination regimen. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured result limits a blanket claim that every relevant drug concentration must rise. organism: Sixty healthy Chinese participants across five groups tissue_or_cell_type: Simvastatin and fenofibrate exposure experimental_model: Open-label randomized parallel pharmacokinetic study limitations: Short, small healthy-volunteer study. Absence of an obvious interaction here does not establish unrestricted long-term safety in patients. exposure: Single-dose and seven-day repeated treatment; berberine chloride alone or combined evidence_span: {"source_cache": "artifacts/berberine-research/30587933.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be", "start_char": 0, "end_char": 2118, "text_sha256": "f82b466cc2942fd70940935e1fa42174f135036017a589bc7fa86388e6f9e4be"} [berberine-p30587933] Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. (2019). https://pubmed.ncbi.nlm.nih.gov/30587933/ DOI: 10.2147/dddt.s185487

duration

Not applicable

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Review of human pharmacogenetic and pharmacokinetic studies

exposure

SLCO1B1 c.521T>C, protein p.V174A, rs4149056

limitations

This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship.

organism

Review of human pharmacogenetic and pharmacokinetic studies

plain_language

The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.

primary_references

Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857

route

Oral statins

tissue

Hepatic uptake, plasma statin concentration and skeletal muscle injury

OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 68–77

Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## oatp1b1-activity-lowers-statin-myopathy-risk The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins. Model/species: Review of human pharmacogenetic and pharmacokinetic studies Tissue/system: Hepatic uptake, plasma statin concentration and skeletal muscle injury Exposure: SLCO1B1 c.521T>C, protein p.V174A, rs4149056 Route: Oral statins Duration: Not applicable Limits: This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship. Primary reference: Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

duration

Single dose with 12-hour sampling

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

4 volunteers with c.521CC, 12 with c.521TC and 16 with c.521TT

exposure

Single 40 mg oral simvastatin dose

limitations

Peak concentration was 200 percent higher and occurred earlier in c.521CC carriers; the four-carrier group is small.

organism

4 volunteers with c.521CC, 12 with c.521TC and 16 with c.521TT

plain_language

Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype.

primary_references

SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. (2006). https://pubmed.ncbi.nlm.nih.gov/17108811/ DOI: 10.1097/01.fpc.0000230416.82349.90

route

Oral

tissue

Plasma simvastatin lactone and active simvastatin acid

OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 57–66

Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## slco1b1-c521cc-raises-simvastatin-acid-exposure Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype. Model/species: 4 volunteers with c.521CC, 12 with c.521TC and 16 with c.521TT Tissue/system: Plasma simvastatin lactone and active simvastatin acid Exposure: Single 40 mg oral simvastatin dose Route: Oral Duration: Single dose with 12-hour sampling Limits: Peak concentration was 200 percent higher and occurred earlier in c.521CC carriers; the four-carrier group is small. Primary reference: SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. (2006). https://pubmed.ncbi.nlm.nih.gov/17108811/ DOI: 10.1097/01.fpc.0000230416.82349.90 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.