Nutrient chapter

Atorvastatin

Atorvastatin. Species, exposure and limitations are retained in each linked claim.

45 recorded mechanisms · 0 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.
Atorvastatin → HMG-CoA reductase (HMGCR) source_derived_draftungraded
Experimental context and source evidence
duration
Not applicable
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins
exposure
Statin-enzyme complexes, inhibition constants in the nanomolar range
limitations
The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes.
organism
Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins
plain_language
Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.
primary_references
Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344
route
Structural
tissue
Enzyme active-site occupancy
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 13–22
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-hmgcr-occupancy Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site. Model/species: Catalytic portion of human HMG-CoA reductase, X-ray structures with six statins Tissue/system: Enzyme active-site occupancy Exposure: Statin-enzyme complexes, inhibition constants in the nanomolar range Route: Structural Duration: Not applicable Limits: The abstract reports structures with six statins without naming them, so this is a class binding mode rather than an atorvastatin-specific structure. Several catalytically relevant residues near the carboxyl terminus are disordered in the complexes. Primary reference: Structural mechanism for statin inhibition of HMG-CoA reductase. (2001). https://pubmed.ncbi.nlm.nih.gov/11349148/ DOI: 10.1126/science.1059344 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors.
Mevalonate → Geranylgeranyl diphosphate / GGPP source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Review of mammalian mevalonate-pathway regulation
exposure
Not applicable
limitations
A review of regulatory architecture, not a measurement of any one statin's effect on any one isoprenoid pool.
organism
Review of mammalian mevalonate-pathway regulation
plain_language
The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors.
primary_references
Regulation of the mevalonate pathway. (1990). https://pubmed.ncbi.nlm.nih.gov/1967820/ DOI: 10.1038/343425a0
route
Not applicable
tissue
Isoprenoid and sterol end-products
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 24–32
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
## mevalonate-supplies-isoprenoids The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors. Model/species: Review of mammalian mevalonate-pathway regulation Tissue/system: Isoprenoid and sterol end-products Exposure: Not applicable Route: Not applicable Limits: A review of regulatory architecture, not a measurement of any one statin's effect on any one isoprenoid pool. Primary reference: Regulation of the mevalonate pathway. (1990). https://pubmed.ncbi.nlm.nih.gov/1967820/ DOI: 10.1038/343425a0 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia.
Atorvastatin → LDL cholesterol concentration source_derived_draftungraded
Experimental context and source evidence
duration
16 weeks
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
84 Japanese type 2 diabetic patients with hypercholesterolaemia
exposure
Atorvastatin for 16 weeks, multicentre open-label
limitations
Open-label and without a placebo arm, and responders were defined by reaching an LDL target rather than randomised.
organism
84 Japanese type 2 diabetic patients with hypercholesterolaemia
plain_language
Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia.
primary_references
Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017
route
Oral
tissue
Plasma lipids
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 34–43
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-ldl-cholesterol Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia. Model/species: 84 Japanese type 2 diabetic patients with hypercholesterolaemia Tissue/system: Plasma lipids Exposure: Atorvastatin for 16 weeks, multicentre open-label Route: Oral Duration: 16 weeks Limits: Open-label and without a placebo arm, and responders were defined by reaching an LDL target rather than randomised. Primary reference: Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol.
Atorvastatin → Serum C-reactive protein concentration source_derived_draftungraded
Experimental context and source evidence
duration
16 weeks
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
84 Japanese type 2 diabetic patients with hypercholesterolaemia
exposure
Atorvastatin for 16 weeks
limitations
An inflammatory marker falling alongside cholesterol in an open-label study does not separate an effect on inflammation from an effect of lower lipids.
organism
84 Japanese type 2 diabetic patients with hypercholesterolaemia
plain_language
Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol.
primary_references
Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017
route
Oral
tissue
High-sensitivity C-reactive protein, with plasminogen activator inhibitor 1, monocyte chemotactic protein 1 and interleukin 6 also measured
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 45–54
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-c-reactive-protein Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol. Model/species: 84 Japanese type 2 diabetic patients with hypercholesterolaemia Tissue/system: High-sensitivity C-reactive protein, with plasminogen activator inhibitor 1, monocyte chemotactic protein 1 and interleukin 6 also measured Exposure: Atorvastatin for 16 weeks Route: Oral Duration: 16 weeks Limits: An inflammatory marker falling alongside cholesterol in an open-label study does not separate an effect on inflammation from an effect of lower lipids. Primary reference: Atorvastatin lowers plasma low-density lipoprotein cholesterol and C-reactive protein in Japanese type 2 diabetic patients. (2006). https://pubmed.ncbi.nlm.nih.gov/16324921/ DOI: 10.1016/j.metabol.2005.07.017 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Mevastatin increased endothelial nitric oxide synthase messenger RNA by about 305 percent and protein by about 180 percent in human endothelial cells.
Mevastatin → Human endothelial nitric oxide synthase / eNOS / NOS3 source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Human endothelial cells
exposure
Mevastatin 1 to 10 micromolar
limitations
The statin tested was mevastatin, not atorvastatin, and this is an expression change in cultured cells rather than a vascular outcome.
organism
Human endothelial cells
plain_language
Mevastatin increased endothelial nitric oxide synthase messenger RNA by about 305 percent and protein by about 180 percent in human endothelial cells.
primary_references
Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266
route
In vitro
tissue
Endothelial nitric oxide synthase expression
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 56–65
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
## statin-raises-endothelial-nos Mevastatin increased endothelial nitric oxide synthase messenger RNA by about 305 percent and protein by about 180 percent in human endothelial cells. Model/species: Human endothelial cells Tissue/system: Endothelial nitric oxide synthase expression Exposure: Mevastatin 1 to 10 micromolar Route: In vitro Duration: Not stated here Limits: The statin tested was mevastatin, not atorvastatin, and this is an expression change in cultured cells rather than a vascular outcome. Primary reference: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.
Geranylgeranyl diphosphate / GGPP → Human endothelial nitric oxide synthase / eNOS / NOS3 source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Human endothelial cells
exposure
Geranylgeranyl diphosphate 1 to 10 micromolar, farnesyl diphosphate 5 to 10 micromolar, L-mevalonate 200 micromolar or LDL 1 mg/ml added with mevastatin
limitations
This identifies which isoprenoid carries the effect; it does not establish that geranylgeranyl diphosphate is limiting at ordinary statin doses in a person.
organism
Human endothelial cells
plain_language
Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.
primary_references
Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266
route
In vitro
tissue
Endothelial nitric oxide synthase expression and Rho membrane translocation
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 67–76
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
## ggpp-reverses-the-nos-response Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not. Model/species: Human endothelial cells Tissue/system: Endothelial nitric oxide synthase expression and Rho membrane translocation Exposure: Geranylgeranyl diphosphate 1 to 10 micromolar, farnesyl diphosphate 5 to 10 micromolar, L-mevalonate 200 micromolar or LDL 1 mg/ml added with mevastatin Route: In vitro Duration: Not stated here Limits: This identifies which isoprenoid carries the effect; it does not establish that geranylgeranyl diphosphate is limiting at ordinary statin doses in a person. Primary reference: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Mevastatin inhibited Rho membrane translocation by about 60 percent and Rho GTP-binding activity by about 78 percent, both reversed by geranylgeranyl diphosphate but not by farnesyl diphosphate.
Mevastatin → Rho membrane translocation and GTP binding source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Human endothelial cells
exposure
Mevastatin with or without geranylgeranyl diphosphate or farnesyl diphosphate
limitations
Measured for Rho as a group by immunoblot and GTP-gamma-S binding, not resolved to individual Rho family members.
organism
Human endothelial cells
plain_language
Mevastatin inhibited Rho membrane translocation by about 60 percent and Rho GTP-binding activity by about 78 percent, both reversed by geranylgeranyl diphosphate but not by farnesyl diphosphate.
primary_references
Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266
route
In vitro
tissue
Rho GTPase membrane localisation and nucleotide binding
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 78–87
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
## statin-inhibits-rho-membrane-translocation Mevastatin inhibited Rho membrane translocation by about 60 percent and Rho GTP-binding activity by about 78 percent, both reversed by geranylgeranyl diphosphate but not by farnesyl diphosphate. Model/species: Human endothelial cells Tissue/system: Rho GTPase membrane localisation and nucleotide binding Exposure: Mevastatin with or without geranylgeranyl diphosphate or farnesyl diphosphate Route: In vitro Duration: Not stated here Limits: Measured for Rho as a group by immunoblot and GTP-gamma-S binding, not resolved to individual Rho family members. Primary reference: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Statin treatment reduced host protein prenylation including prenylation of Rho GTPases, and reduced respiratory syncytial virus infection in vitro through combined cholesterol and isoprenoid effects.
Statin therapy as a drug class → Prenylation of Rho-family GTPases source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Live-cell high-content screen in human cell culture
exposure
Statins, and separately perillyl alcohol as a geranylgeranyltransferase inhibitor
limitations
The screen tested statins as a class without attributing the result to atorvastatin, and respiratory syncytial virus infection itself globally upregulated prenylation, so the baseline was not a resting cell.
organism
Live-cell high-content screen in human cell culture
plain_language
Statin treatment reduced host protein prenylation including prenylation of Rho GTPases, and reduced respiratory syncytial virus infection in vitro through combined cholesterol and isoprenoid effects.
primary_references
Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection. (2021). https://pubmed.ncbi.nlm.nih.gov/34716403/ DOI: 10.1038/s42003-021-02754-2
route
In vitro
tissue
Host protein prenylation and virus production
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 89–98
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
## statin-reduces-rho-gtpase-prenylation Statin treatment reduced host protein prenylation including prenylation of Rho GTPases, and reduced respiratory syncytial virus infection in vitro through combined cholesterol and isoprenoid effects. Model/species: Live-cell high-content screen in human cell culture Tissue/system: Host protein prenylation and virus production Exposure: Statins, and separately perillyl alcohol as a geranylgeranyltransferase inhibitor Route: In vitro Duration: Not stated here Limits: The screen tested statins as a class without attributing the result to atorvastatin, and respiratory syncytial virus infection itself globally upregulated prenylation, so the baseline was not a resting cell. Primary reference: Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection. (2021). https://pubmed.ncbi.nlm.nih.gov/34716403/ DOI: 10.1038/s42003-021-02754-2 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Loss of Rac1 activity strongly inhibited respiratory syncytial virus through a decrease in F protein surface expression.
RAC1 → Respiratory syncytial virus F protein surface expression source_derived_draftungraded
Experimental context and source evidence
duration
Not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Human cell culture
exposure
Rac1 activity loss under statin or geranylgeranyltransferase inhibition
limitations
Rac1 was the strongest of the Rho-family GTPases assayed in that study; the others were not equivalent.
organism
Human cell culture
plain_language
Loss of Rac1 activity strongly inhibited respiratory syncytial virus through a decrease in F protein surface expression.
primary_references
Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection. (2021). https://pubmed.ncbi.nlm.nih.gov/34716403/ DOI: 10.1038/s42003-021-02754-2
route
In vitro
tissue
Rho-family GTPase activity and viral fusion protein surface expression
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 100–109
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
## rac1-supports-viral-f-protein-surface-expression Loss of Rac1 activity strongly inhibited respiratory syncytial virus through a decrease in F protein surface expression. Model/species: Human cell culture Tissue/system: Rho-family GTPase activity and viral fusion protein surface expression Exposure: Rac1 activity loss under statin or geranylgeranyltransferase inhibition Route: In vitro Duration: Not stated here Limits: Rac1 was the strongest of the Rho-family GTPases assayed in that study; the others were not equivalent. Primary reference: Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection. (2021). https://pubmed.ncbi.nlm.nih.gov/34716403/ DOI: 10.1038/s42003-021-02754-2 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Atorvastatin at its half-maximal inhibitory concentration reduced the viability of proliferating murine C2C12 myoblasts.
Atorvastatin → C2C12 myoblast viability source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.
Geranylgeraniol / GGOH → C2C12 myoblast viability source_derived_draftungraded
Experimental context and source evidence
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
Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin
limitations
Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact.
organism
Murine C2C12 myoblasts
plain_language
Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.
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
Prenylation of RAP1 and muscle cell viability
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 122–131
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
## geranylgeraniol-rescues-statin-myotoxicity Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1. Model/species: Murine C2C12 myoblasts Tissue/system: Prenylation of RAP1 and muscle cell viability Exposure: Geranylgeraniol, farnesol, mevalonate or water-soluble cholesterol co-treatment with statin Route: In vitro Duration: Not stated here Limits: Cholesterol rescued only methyl-beta-cyclodextrin toxicity, and geranylgeranyltransferase inhibition with GGTI-286 could not be reversed by geranylgeraniol, so the rescue requires the transferase to be intact. 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.
Complete structured claim and evidence
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.
SLCO1B1 rs4363657 variant → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.
Human CYP3A4 activity, probe and compartment specified → Plasma atorvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Not applicable
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Human liver microsomes and human recombinant CYP3A enzymes
exposure
Atorvastatin, enzyme kinetics showing substrate inhibition
limitations
The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition.
organism
Human liver microsomes and human recombinant CYP3A enzymes
plain_language
Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.
primary_references
Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391
route
In vitro
tissue
Hepatic oxidative metabolism
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 144–153
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
## cyp3a4-clears-atorvastatin Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5. Model/species: Human liver microsomes and human recombinant CYP3A enzymes Tissue/system: Hepatic oxidative metabolism Exposure: Atorvastatin, enzyme kinetics showing substrate inhibition Route: In vitro Duration: Not applicable Limits: The authors conclude the CYP3A5 polymorphism is therefore unlikely to be an important source of between-person variation in atorvastatin disposition. Primary reference: Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. (2008). https://pubmed.ncbi.nlm.nih.gov/18720283/ DOI: 10.1080/00498250802334391 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.
Clarithromycin → Plasma atorvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Two phases separated by at least 14 days
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
exposure
Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days
limitations
A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here.
organism
23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors
plain_language
Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.
primary_references
Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942
route
Oral
tissue
Plasma atorvastatin acid and atorvastatin lactone
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 155–164
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
## clarithromycin-raises-atorvastatin-exposure Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5. Model/species: 23 healthy volunteers, 10 CYP3A5*1 expressors and 13 nonexpressors Tissue/system: Plasma atorvastatin acid and atorvastatin lactone Exposure: Single oral atorvastatin 20 mg, with and without clarithromycin 500 mg twice daily for 5 days Route: Oral Duration: Two phases separated by at least 14 days Limits: A single-dose interaction study in healthy volunteers, and the abstract does not state the size of the exposure change here. Primary reference: Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. (2011). https://pubmed.ncbi.nlm.nih.gov/21950641/ DOI: 10.1592/phco.31.10.942 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol.
Atorvastatin → Plasma coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
duration
Crossover phases, length not stated here
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
19 Japanese patients with heterozygous familial hypercholesterolaemia
exposure
Atorvastatin 20 mg or pitavastatin 4 mg, open randomised four-phase crossover
limitations
Pitavastatin lowered coenzyme Q10 by 7.7 percent without reaching significance, so this is a difference in degree; no adverse events or liver or muscle enzyme abnormalities were observed with either statin, and the authors state it remains to be seen whether the change relates to long-term safety.
organism
19 Japanese patients with heterozygous familial hypercholesterolaemia
plain_language
Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol.
primary_references
Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia. (2008). https://pubmed.ncbi.nlm.nih.gov/17957184/ DOI: 10.1038/sj.clpt.6100396
route
Oral
tissue
Plasma coenzyme Q10
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 166–175
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-lowers-plasma-coenzyme-q10 Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol. Model/species: 19 Japanese patients with heterozygous familial hypercholesterolaemia Tissue/system: Plasma coenzyme Q10 Exposure: Atorvastatin 20 mg or pitavastatin 4 mg, open randomised four-phase crossover Route: Oral Duration: Crossover phases, length not stated here Limits: Pitavastatin lowered coenzyme Q10 by 7.7 percent without reaching significance, so this is a difference in degree; no adverse events or liver or muscle enzyme abnormalities were observed with either statin, and the authors state it remains to be seen whether the change relates to long-term safety. Primary reference: Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia. (2008). https://pubmed.ncbi.nlm.nih.gov/17957184/ DOI: 10.1038/sj.clpt.6100396 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Muscle ubiquinone fell significantly in the simvastatin arm and did not fall in the atorvastatin or placebo arms.
Atorvastatin → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Statin therapy was associated with a 9 percent increased risk of incident diabetes across 13 randomised trials.
Statin therapy as a drug class → Incident diabetes mellitus source_derived_draftungraded
Experimental context and source evidence
duration
Mean 4 years
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Meta-analysis of 13 statin trials with 91,140 participants, of whom 4,278 developed diabetes
exposure
Statin therapy in trials of more than 1,000 patients lasting more than one year
limitations
A class-level association across statins and doses, not an atorvastatin-specific or mechanism-specific result, and derived from trials whose primary endpoints were cardiovascular.
organism
Meta-analysis of 13 statin trials with 91,140 participants, of whom 4,278 developed diabetes
plain_language
Statin therapy was associated with a 9 percent increased risk of incident diabetes across 13 randomised trials.
primary_references
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. (2010). https://pubmed.ncbi.nlm.nih.gov/20167359/ DOI: 10.1016/S0140-6736(09)61965-6
route
Oral
tissue
New-onset diabetes mellitus
Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 188–197
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
## statin-therapy-and-incident-diabetes Statin therapy was associated with a 9 percent increased risk of incident diabetes across 13 randomised trials. Model/species: Meta-analysis of 13 statin trials with 91,140 participants, of whom 4,278 developed diabetes Tissue/system: New-onset diabetes mellitus Exposure: Statin therapy in trials of more than 1,000 patients lasting more than one year Route: Oral Duration: Mean 4 years Limits: A class-level association across statins and doses, not an atorvastatin-specific or mechanism-specific result, and derived from trials whose primary endpoints were cardiovascular. Primary reference: Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. (2010). https://pubmed.ncbi.nlm.nih.gov/20167359/ DOI: 10.1016/S0140-6736(09)61965-6 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
All seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.
Human electron transfer flavoprotein dehydrogenase / ETFDH → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coq10-research/17412732.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494", "start_char": 0, "end_char": 1533, "text_sha256": "38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494"}
experimental_model
Genetic case series and muscle biochemistry
exposure
Biallelic ETFDH variants
limitations
Secondary CoQ depletion reported in this cohort; later cohorts did not reproduce universal muscle depletion.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Seven patients from five families
plain_language
A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.
primary_references
[coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054
tissue_or_cell_type
ETFDH-associated myopathy
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1061–1072
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic case series and muscle biochemistry · source_derived_draft · unverified_draft
### coq10-etfdh-coq-low All seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group. organism: Seven patients from five families tissue_or_cell_type: ETFDH-associated myopathy experimental_model: Genetic case series and muscle biochemistry limitations: Secondary CoQ depletion reported in this cohort; later cohorts did not reproduce universal muscle depletion. exposure: Biallelic ETFDH variants evidence_span: {"source_cache": "artifacts/coq10-research/17412732.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494", "start_char": 0, "end_char": 1533, "text_sha256": "38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494"} [coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054
Complete structured claim and evidence
Muscle CoQ was elevated in the 34-patient cohort but not significantly different from controls after normalization to citrate synthase.
Human electron transfer flavoprotein dehydrogenase / ETFDH → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coq10-research/23628458.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6", "start_char": 0, "end_char": 1706, "text_sha256": "4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6"}
experimental_model
Muscle HPLC, citrate-synthase normalization and mtDNA measurements
exposure
Genetically defined MADD cohort
limitations
Different variants/cohort from the earlier report; bulk concentration and concentration per mitochondrial mass are different measurements.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
34 riboflavin-responsive ETFDH-MADD patients
plain_language
More mitochondria can change a bulk tissue measurement without increasing CoQ per mitochondrial mass.
primary_references
[coq10-p23628458] Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation. (2013). https://pubmed.ncbi.nlm.nih.gov/23628458/ DOI: 10.1016/j.ymgme.2013.04.007
tissue_or_cell_type
Muscle CoQ and mitochondrial mass
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1074–1085
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Muscle HPLC, citrate-synthase normalization and mtDNA measurements · source_derived_draft · unverified_draft
### coq10-etfdh-coq-normalized Muscle CoQ was elevated in the 34-patient cohort but not significantly different from controls after normalization to citrate synthase. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More mitochondria can change a bulk tissue measurement without increasing CoQ per mitochondrial mass. organism: 34 riboflavin-responsive ETFDH-MADD patients tissue_or_cell_type: Muscle CoQ and mitochondrial mass experimental_model: Muscle HPLC, citrate-synthase normalization and mtDNA measurements limitations: Different variants/cohort from the earlier report; bulk concentration and concentration per mitochondrial mass are different measurements. exposure: Genetically defined MADD cohort evidence_span: {"source_cache": "artifacts/coq10-research/23628458.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6", "start_char": 0, "end_char": 1706, "text_sha256": "4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6"} [coq10-p23628458] Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation. (2013). https://pubmed.ncbi.nlm.nih.gov/23628458/ DOI: 10.1016/j.ymgme.2013.04.007
Complete structured claim and evidence
The 2022 trial found no effect on myalgia; individual changes in muscle CoQ did not correlate with changes in symptom intensity.
Coenzyme Q10 / CoQ10 redox system → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"}
experimental_model
Randomized placebo-controlled muscle-biopsy supplementation trial
exposure
CoQ10 400 mg/day for eight weeks
limitations
One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
37 simvastatin-treated adults with or without myalgia
plain_language
A measured muscle pool and the pain outcome must be assessed separately.
primary_references
[coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698
tissue_or_cell_type
Muscle CoQ, mitochondrial function and symptoms
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 996–1007
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled muscle-biopsy supplementation trial · source_derived_draft · unverified_draft
### coq10-statin-2022-pain-null The 2022 trial found no effect on myalgia; individual changes in muscle CoQ did not correlate with changes in symptom intensity. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured muscle pool and the pain outcome must be assessed separately. organism: 37 simvastatin-treated adults with or without myalgia tissue_or_cell_type: Muscle CoQ, mitochondrial function and symptoms experimental_model: Randomized placebo-controlled muscle-biopsy supplementation trial limitations: One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse. exposure: CoQ10 400 mg/day for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"} [coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698
Complete structured claim and evidence
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.
Simvastatin → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
CoQ supplementation did not increase muscle CoQ or alter measured mitochondrial respiratory function, content or reactive-oxygen-species production.
Coenzyme Q10 / CoQ10 redox system → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"}
experimental_model
Randomized placebo-controlled muscle-biopsy supplementation trial
exposure
CoQ10 400 mg/day for eight weeks
limitations
One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
37 simvastatin-treated adults with or without myalgia
plain_language
Taking more did not ensure delivery or functional change in the sampled muscle.
primary_references
[coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698
tissue_or_cell_type
Muscle CoQ, mitochondrial function and symptoms
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 983–994
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled muscle-biopsy supplementation trial · source_derived_draft · unverified_draft
### coq10-statin-muscle-repletion-null CoQ supplementation did not increase muscle CoQ or alter measured mitochondrial respiratory function, content or reactive-oxygen-species production. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Taking more did not ensure delivery or functional change in the sampled muscle. organism: 37 simvastatin-treated adults with or without myalgia tissue_or_cell_type: Muscle CoQ, mitochondrial function and symptoms experimental_model: Randomized placebo-controlled muscle-biopsy supplementation trial limitations: One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse. exposure: CoQ10 400 mg/day for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"} [coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698
Complete structured claim and evidence
Ubiquinol did not reduce pain severity or interference versus placebo in confirmed simvastatin myalgia.
Reduced CoQ10 → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Pain severity and interference improved relative to placebo after 30 days of CoQ in the 50-patient study.
Coenzyme Q10 / CoQ10 redox system → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/25375075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4", "start_char": 0, "end_char": 1622, "text_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4"}
experimental_model
Randomized placebo-controlled study
exposure
CoQ10 50 mg twice daily for 30 days
limitations
Small short study; symptoms were not confirmed by a blinded statin-placebo lead-in as in the later trial.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
50 statin-treated patients reporting mild-to-moderate muscle symptoms
plain_language
One trial found less muscle pain with added CoQ.
primary_references
[coq10-p25375075] Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. (2014). https://pubmed.ncbi.nlm.nih.gov/25375075/ DOI: 10.12659/msm.890777
tissue_or_cell_type
Brief Pain Inventory scores
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1152–1163
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled study · source_derived_draft · unverified_draft
### coq10-statin-pain-positive Pain severity and interference improved relative to placebo after 30 days of CoQ in the 50-patient study. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: One trial found less muscle pain with added CoQ. organism: 50 statin-treated patients reporting mild-to-moderate muscle symptoms tissue_or_cell_type: Brief Pain Inventory scores experimental_model: Randomized placebo-controlled study limitations: Small short study; symptoms were not confirmed by a blinded statin-placebo lead-in as in the later trial. exposure: CoQ10 50 mg twice daily for 30 days evidence_span: {"source_cache": "artifacts/coq10-research/25375075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4", "start_char": 0, "end_char": 1622, "text_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4"} [coq10-p25375075] Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. (2014). https://pubmed.ncbi.nlm.nih.gov/25375075/ DOI: 10.12659/msm.890777
Complete structured claim and evidence
Simvastatin, alone or with ezetimibe, lowered plasma CoQ; CoQ change correlated with LDL-cholesterol change and the CoQ-to-LDL ratio increased.
Simvastatin → Plasma coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Respiratory-chain enzyme and citrate-synthase activities were lower in the selected simvastatin subgroup with marked muscle CoQ decline.
Simvastatin → Mitochondrial respiratory electron transfer source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
After four weeks, serum ubiquinone decreased while muscle ubiquinone increased; no participant developed myopathy.
Simvastatin → Muscle coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Simvastatin inhibits HMG-CoA reductase, an upstream enzyme in the mevalonate pathway shared by sterol and CoQ precursor production.
Simvastatin → HMG-CoA reductase (HMGCR) source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The original monacolin K study prepared acid forms by saponifying lactones in 0.1 N NaOH at 50 degrees C for two hours.
Lovastatin / monacolin K lactone → Lovastatin hydroxy acid / monacolin KA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary PDF, Methods p334
experimental_model
Chemical preparation for the 1980 biochemical study.
limitations
These laboratory conditions are not a claim about the rate or enzyme of human conversion.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
Opening the lactone ring produces a different chemical form.
primary_references
[7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical preparation for the 1980 biochemical study. · source_derived_draft · unverified_draft
## red-yeast-rice-acid-preparation Opening the lactone ring produces a different chemical form. The original monacolin K study prepared acid forms by saponifying lactones in 0.1 N NaOH at 50 degrees C for two hours. Model: Chemical preparation for the 1980 biochemical study. Limitations: These laboratory conditions are not a claim about the rate or enzyme of human conversion. Evidence access: Primary PDF, Methods p334 [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
Complete structured claim and evidence
The 1990 human lovastatin report observed reductions in circulating CoQ10 during drug exposure in five hospitalized patients and a separately monitored volunteer.
Lovastatin / monacolin K lactone → Plasma coenzyme Q10 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Small uncontrolled clinical series, including pre-existing cardiac disease.
limitations
Does not establish causal cardiomyopathy, tissue deficiency or the same effect from a specified red yeast rice product.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
A constituent has human CoQ observations, with major study limitations.
primary_references
[2247468] Lovastatin decreases coenzyme Q levels in humans. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2247468/ · DOI 10.1073/pnas.87.22.8931
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small uncontrolled clinical series, including pre-existing cardiac disease. · source_derived_draft · unverified_draft
## red-yeast-rice-human-lovastatin-coq A constituent has human CoQ observations, with major study limitations. The 1990 human lovastatin report observed reductions in circulating CoQ10 during drug exposure in five hospitalized patients and a separately monitored volunteer. Model: Small uncontrolled clinical series, including pre-existing cardiac disease. Limitations: Does not establish causal cardiomyopathy, tissue deficiency or the same effect from a specified red yeast rice product. Evidence access: Primary abstract [2247468] Lovastatin decreases coenzyme Q levels in humans. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2247468/ · DOI 10.1073/pnas.87.22.8931
Complete structured claim and evidence
Human HMG-CoA reductase catalyzes mevalonate formation; substrate/cofactor-bound structures locate HMG-CoA and the nicotinamide cofactor in the catalytic domain.
HMG-CoA reductase (HMGCR) → Mevalonate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human recombinant catalytic-domain crystallography and biochemical background.
limitations
Shared human machinery; the source is not an experiment administering red yeast rice.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
This enzyme supplies a shared precursor pathway.
primary_references
[10698924] Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10698924/ · DOI 10.1093/emboj/19.5.819
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant catalytic-domain crystallography and biochemical background. · source_derived_draft · unverified_draft
## red-yeast-rice-human-mevalonate-machinery This enzyme supplies a shared precursor pathway. Human HMG-CoA reductase catalyzes mevalonate formation; substrate/cofactor-bound structures locate HMG-CoA and the nicotinamide cofactor in the catalytic domain. Model: Human recombinant catalytic-domain crystallography and biochemical background. Limitations: Shared human machinery; the source is not an experiment administering red yeast rice. Evidence access: Primary abstract [10698924] Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10698924/ · DOI 10.1093/emboj/19.5.819
Complete structured claim and evidence
Monacolin K inhibited lipid labeling from acetate or HMG-CoA, but did not inhibit incorporation from supplied mevalonate at concentrations up to 10 mM.
Lovastatin / monacolin K lactone → Mevalonate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary PDF, p335 visually inspected
experimental_model
Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested.
limitations
A biochemical bypass is not a clinical repletion strategy; the 10 mM figure applies to tested monacolin concentrations, not human exposure.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
Supplying the downstream intermediate bypassed the inhibited step in this assay.
primary_references
[7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested. · source_derived_draft · unverified_draft
## red-yeast-rice-mevalonate-bypass Supplying the downstream intermediate bypassed the inhibited step in this assay. Monacolin K inhibited lipid labeling from acetate or HMG-CoA, but did not inhibit incorporation from supplied mevalonate at concentrations up to 10 mM. Model: Rat liver cell-free nonsaponifiable-lipid synthesis; lactone and acid preparations tested. Limitations: A biochemical bypass is not a clinical repletion strategy; the 10 mM figure applies to tested monacolin concentrations, not human exposure. Evidence access: Primary PDF, p335 visually inspected [7380744] Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. · 1980 · https://pubmed.ncbi.nlm.nih.gov/7380744/ · DOI 10.7164/antibiotics.33.334
Complete structured claim and evidence
The 28-brand analytical study treated monacolin K in red yeast rice as chemically identical to lovastatin.
Red yeast rice → Lovastatin / monacolin K lactone source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
2017 commercial-product chemical analysis.
limitations
Chemical identity does not make the whole mixture identical to a lovastatin tablet or establish equal exposure.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
A constituent can be the same molecule as a prescription drug.
primary_references
[28641460] Variability in strength of red yeast rice supplements purchased from mainstream retailers. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28641460/ · DOI 10.1177/2047487317715714
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 12–18
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2017 commercial-product chemical analysis. · source_derived_draft · unverified_draft
## red-yeast-rice-monacolin-identity A constituent can be the same molecule as a prescription drug. The 28-brand analytical study treated monacolin K in red yeast rice as chemically identical to lovastatin. Model: 2017 commercial-product chemical analysis. Limitations: Chemical identity does not make the whole mixture identical to a lovastatin tablet or establish equal exposure. Evidence access: Primary abstract [28641460] Variability in strength of red yeast rice supplements purchased from mainstream retailers. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28641460/ · DOI 10.1177/2047487317715714
Complete structured claim and evidence
Monacolin K was undetected in two of 28 brands; the other 26 ranged from 0.09 to 5.48 mg per 1,200 mg red yeast rice.
Red yeast rice → Lovastatin / monacolin K lactone source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
UHPLC-based analysis of products purchased for the 2017 study.
limitations
A historical sample, not a measurement of current products or batches.
nutrient_topic
Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice
plain_language
Equal masses of product delivered very different measured amounts.
primary_references
[28641460] Variability in strength of red yeast rice supplements purchased from mainstream retailers. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28641460/ · DOI 10.1177/2047487317715714
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · UHPLC-based analysis of products purchased for the 2017 study. · source_derived_draft · unverified_draft
## red-yeast-rice-monacolin-variability Equal masses of product delivered very different measured amounts. Monacolin K was undetected in two of 28 brands; the other 26 ranged from 0.09 to 5.48 mg per 1,200 mg red yeast rice. Model: UHPLC-based analysis of products purchased for the 2017 study. Limitations: A historical sample, not a measurement of current products or batches. Evidence access: Primary abstract [28641460] Variability in strength of red yeast rice supplements purchased from mainstream retailers. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28641460/ · DOI 10.1177/2047487317715714
Complete structured claim and evidence
A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.
Rifampicin → Plasma atorvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Single dose, sampling to 24 hours
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
11 healthy human volunteers, randomised crossover
exposure
Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days
limitations
Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause.
organism
11 healthy human volunteers, randomised crossover
plain_language
A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.
primary_references
The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038
route
Oral atorvastatin with intravenous rifampicin
tissue
Plasma atorvastatin acid and its hydroxy metabolites
OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 13–22
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
## rifampicin-raises-atorvastatin-exposure A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers. Model/species: 11 healthy human volunteers, randomised crossover Tissue/system: Plasma atorvastatin acid and its hydroxy metabolites Exposure: Two 40 mg oral atorvastatin doses one week apart, with one 30-minute intravenous infusion of 600 mg rifampicin on one of the two study days Route: Oral atorvastatin with intravenous rifampicin Duration: Single dose, sampling to 24 hours Limits: Rifampicin is used here as a model hepatic uptake inhibitor and is not selective for OATP1B1; the lactone forms rose less than the acid, and a single intravenous dose avoids the enzyme induction that repeated oral rifampicin would cause. Primary reference: The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.
Human OATP1B1 / SLCO1B1 → Plasma atorvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Single dose in both designs
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype
exposure
Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another
limitations
This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants.
organism
Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype
plain_language
OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.
primary_references
The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038
route
Oral atorvastatin
tissue
Hepatic sinusoidal uptake and systemic plasma exposure
OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 24–33
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-atorvastatin-exposure OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration. Model/species: Healthy human volunteers, by pharmacological inhibition and by reduced-function genotype Tissue/system: Hepatic sinusoidal uptake and systemic plasma exposure Exposure: Rifampicin inhibition in one study and the SLCO1B1 c.521CC genotype in another Route: Oral atorvastatin Duration: Single dose in both designs Limits: This is the mechanistic reading shared by an inhibitor study and a genotype study rather than a single measurement of transporter activity against exposure; neither study measured OATP1B1 activity directly in the participants. Primary reference: The effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. (2007). https://pubmed.ncbi.nlm.nih.gov/17192770/ DOI: 10.1038/sj.clpt.6100038 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.
SLCO1B1 c.521T>C reduced-function variant → Plasma atorvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Single dose with 48-hour sampling
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT
exposure
Single 20 mg oral atorvastatin dose
limitations
Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison.
organism
32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT
plain_language
Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.
primary_references
Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220
route
Oral
tissue
Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours
OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 35–44
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-atorvastatin-exposure Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype. Model/species: 32 healthy volunteers, 4 with c.521CC, 12 with c.521TC and 16 with c.521TT Tissue/system: Plasma atorvastatin area under the concentration-time curve from 0 to 48 hours Exposure: Single 20 mg oral atorvastatin dose Route: Oral Duration: Single dose with 48-hour sampling Limits: Only four participants carried the c.521CC genotype, and 2-hydroxyatorvastatin exposure was 100 percent greater in the same comparison. Primary reference: Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin.
SLCO1B1 c.521T>C reduced-function variant → Plasma rosuvastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
Single dose with 48-hour sampling
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
The same 32 healthy volunteers
exposure
Single 10 mg oral rosuvastatin dose, one week apart from the atorvastatin dose
limitations
A within-study comparison of two statins at different doses, so the ratio of effects is not a dose-matched comparison.
organism
The same 32 healthy volunteers
plain_language
The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin.
primary_references
Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220
route
Oral
tissue
Plasma rosuvastatin area under the concentration-time curve and peak concentration
OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 46–55
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-rosuvastatin-exposure-less The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin. Model/species: The same 32 healthy volunteers Tissue/system: Plasma rosuvastatin area under the concentration-time curve and peak concentration Exposure: Single 10 mg oral rosuvastatin dose, one week apart from the atorvastatin dose Route: Oral Duration: Single dose with 48-hour sampling Limits: A within-study comparison of two statins at different doses, so the ratio of effects is not a dose-matched comparison. Primary reference: Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. (2007). https://pubmed.ncbi.nlm.nih.gov/17473846/ DOI: 10.1038/sj.clpt.6100220 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Volunteers with the SLCO1B1 c.521CC genotype had 221 percent greater plasma exposure to active simvastatin acid than those with the c.521TT genotype.
SLCO1B1 c.521T>C reduced-function variant → Plasma simvastatin exposure source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
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.
Human OATP1B1 / SLCO1B1 → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.
Simvastatin 80 mg daily → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Gemfibrozil increased the plasma exposure of active simvastatin acid by 185 percent and its peak concentration by 112 percent.
Gemfibrozil → Plasma simvastatin exposure source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.
Plasma simvastatin exposure → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
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.
Complete structured claim and evidence
Gemfibrozil raised the plasma exposure of cerivastatin to 559 percent of control, with a range across subjects of 138 to 995 percent.
Gemfibrozil → Plasma cerivastatin exposure source_derived_draftungraded
Experimental context and source evidence
duration
3 days of gemfibrozil, 24 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, randomised double-blind crossover
exposure
Gemfibrozil 600 mg twice daily for 3 days, then a single 0.3 mg cerivastatin dose
limitations
Metabolite M-23 exposure fell to 22 percent of control while the parent and other metabolites rose, so the interaction shifts the metabolic route rather than simply slowing clearance. Between-subject variation was wide.
organism
10 healthy volunteers, randomised double-blind crossover
plain_language
Gemfibrozil raised the plasma exposure of cerivastatin to 559 percent of control, with a range across subjects of 138 to 995 percent.
primary_references
Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469
route
Oral
tissue
Plasma cerivastatin, cerivastatin lactone and its metabolites
Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 46–55
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-cerivastatin-exposure Gemfibrozil raised the plasma exposure of cerivastatin to 559 percent of control, with a range across subjects of 138 to 995 percent. Model/species: 10 healthy volunteers, randomised double-blind crossover Tissue/system: Plasma cerivastatin, cerivastatin lactone and its metabolites Exposure: Gemfibrozil 600 mg twice daily for 3 days, then a single 0.3 mg cerivastatin dose Route: Oral Duration: 3 days of gemfibrozil, 24 hours of sampling Limits: Metabolite M-23 exposure fell to 22 percent of control while the parent and other metabolites rose, so the interaction shifts the metabolic route rather than simply slowing clearance. Between-subject variation was wide. Primary reference: Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence
Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear.
Plasma cerivastatin exposure → Statin-associated muscle pain source_derived_draftungraded
Experimental context and source evidence
duration
Not applicable
evidence_access
Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
experimental_model
Stated as the background to a 10-volunteer pharmacokinetic study
exposure
Gemfibrozil with cerivastatin
limitations
This is the study's framing of an established clinical association rather than a measurement made in it; no muscle outcome was recorded in the ten volunteers.
organism
Stated as the background to a 10-volunteer pharmacokinetic study
plain_language
Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear.
primary_references
Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469
route
Oral
tissue
Skeletal muscle injury risk during combined treatment
Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 57–66
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
## cerivastatin-exposure-and-rhabdomyolysis-risk Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear. Model/species: Stated as the background to a 10-volunteer pharmacokinetic study Tissue/system: Skeletal muscle injury risk during combined treatment Exposure: Gemfibrozil with cerivastatin Route: Oral Duration: Not applicable Limits: This is the study's framing of an established clinical association rather than a measurement made in it; no muscle outcome was recorded in the ten volunteers. Primary reference: Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)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. · unverified_draftRead preserved source
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22)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. · unverified_draftRead preserved source
Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22)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. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

ETFDH-related myopathy: depleted muscle CoQ versus no deficit after mitochondrial normalizationThe 2007 series reported low muscle CoQ in every patient; the 2013 study explicitly revisited that conclusion and found an elevated bulk pool with no deficit after citrate-synthase normalization. This challenges a universal secondary-CoQ-deficiency interpretation of ETFDH disease.Read the recorded disagreement
Statin-associated muscle pain: improvement in one trial, absent in othersThe 2014 study found pain relief, whereas the 2015 trial found no benefit after symptoms were confirmed with blinded simvastatin/placebo exposure. A 2022 trial also found no pain benefit or increase in muscle CoQ. These challenge a general claim of CoQ efficacy for statin-associated muscle pain; selection, formulation, dose and duration differed.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Atorvastatin

The mechanisms

Statins occupy a portion of the HMG-CoA binding site of HMG-CoA reductase and block access of the substrate to the active site.

The mevalonate pathway produces isoprenoids required for functions ranging from cholesterol synthesis to growth control, under feedback regulation that also governs low-density-lipoprotein receptors.

Sixteen weeks of atorvastatin reduced total cholesterol and low-density-lipoprotein cholesterol in type 2 diabetic patients with hypercholesterolaemia.

Atorvastatin significantly reduced high-sensitivity C-reactive protein alongside the reduction in cholesterol.

Mevastatin increased endothelial nitric oxide synthase messenger RNA by about 305 percent and protein by about 180 percent in human endothelial cells.

Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.

Mevastatin inhibited Rho membrane translocation by about 60 percent and Rho GTP-binding activity by about 78 percent, both reversed by geranylgeranyl diphosphate but not by farnesyl diphosphate.

Statin treatment reduced host protein prenylation including prenylation of Rho GTPases, and reduced respiratory syncytial virus infection in vitro through combined cholesterol and isoprenoid effects.

Loss of Rac1 activity strongly inhibited respiratory syncytial virus through a decrease in F protein surface expression.

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

Geranylgeraniol fully reverted statin-mediated loss of myoblast viability, while water-soluble cholesterol did not, and statins caused loss of prenylated RAP1.

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.

Atorvastatin is metabolised mainly by CYP3A4 to para- and ortho-hydroxyatorvastatin, with intrinsic clearance 2.4-fold and 5.0-fold that of CYP3A5.

Clarithromycin was given with atorvastatin to test its effect on atorvastatin pharmacokinetics in healthy volunteers genotyped for CYP3A5.

Atorvastatin 20 mg reduced plasma coenzyme Q10 by 26.1 percent, while pitavastatin 4 mg did not, despite comparable reductions in cholesterol.

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

Statin therapy was associated with a 9 percent increased risk of incident diabetes across 13 randomised trials.

All seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.

Muscle CoQ was elevated in the 34-patient cohort but not significantly different from controls after normalization to citrate synthase.

The 2022 trial found no effect on myalgia; individual changes in muscle CoQ did not correlate with changes in symptom intensity.

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.

CoQ supplementation did not increase muscle CoQ or alter measured mitochondrial respiratory function, content or reactive-oxygen-species production.

Ubiquinol did not reduce pain severity or interference versus placebo in confirmed simvastatin myalgia.

Pain severity and interference improved relative to placebo after 30 days of CoQ in the 50-patient study.

Simvastatin, alone or with ezetimibe, lowered plasma CoQ; CoQ change correlated with LDL-cholesterol change and the CoQ-to-LDL ratio increased.

Respiratory-chain enzyme and citrate-synthase activities were lower in the selected simvastatin subgroup with marked muscle CoQ decline.

After four weeks, serum ubiquinone decreased while muscle ubiquinone increased; no participant developed myopathy.

Simvastatin inhibits HMG-CoA reductase, an upstream enzyme in the mevalonate pathway shared by sterol and CoQ precursor production.

The original monacolin K study prepared acid forms by saponifying lactones in 0.1 N NaOH at 50 degrees C for two hours.

The 1990 human lovastatin report observed reductions in circulating CoQ10 during drug exposure in five hospitalized patients and a separately monitored volunteer.

Human HMG-CoA reductase catalyzes mevalonate formation; substrate/cofactor-bound structures locate HMG-CoA and the nicotinamide cofactor in the catalytic domain.

Monacolin K inhibited lipid labeling from acetate or HMG-CoA, but did not inhibit incorporation from supplied mevalonate at concentrations up to 10 mM.

The 28-brand analytical study treated monacolin K in red yeast rice as chemically identical to lovastatin.

Monacolin K was undetected in two of 28 brands; the other 26 ranged from 0.09 to 5.48 mg per 1,200 mg red yeast rice.

A single intravenous dose of rifampicin increased the total plasma exposure of atorvastatin acid by 6.8-fold in healthy volunteers.

OATP1B1 activity lowers plasma atorvastatin exposure by carrying the drug from portal blood into the hepatocyte, so reducing that activity raises the plasma concentration.

Volunteers with the SLCO1B1 c.521CC genotype had 144 percent greater plasma atorvastatin exposure than those with the c.521TT genotype.

The same SLCO1B1 c.521CC genotype raised rosuvastatin exposure by 65 percent, a smaller effect than on atorvastatin, which the authors describe as unexpected for the more hydrophilic statin.

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

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.

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

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

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

Gemfibrozil raised the plasma exposure of cerivastatin to 559 percent of control, with a range across subjects of 138 to 995 percent.

Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear.

Availability and dependencies

The sources

Recorded disagreements

Open questions in this collection