Atorvastatin Induces Bioenergetic Impairment and Oxidative Stress Through Reverse Electron Transport.
Level 5 - mechanism / opinion, no new human data
In vitro bench study using cultured human dermal fibroblasts.
PubMed 41154456 · doi:10.3390/antiox14101147
What was done
Human dermal fibroblasts were treated with atorvastatin (noting high concentrations) to assess cytotoxicity, oxidative stress, and mitochondrial function. Researchers evaluated reactive oxygen species (ROS) production, mitochondrial oxygen consumption rate (OCR), the intracellular ATP/ADP ratio, and respiratory complexes I and III activity, along with the protective effects of Coenzyme Q10 (CoQ10) co-supplementation.
What was found
The abstract reports no quantitative values, effect sizes, or confidence intervals. Directionally, atorvastatin exposure inhibited mitochondrial complexes I and III, triggered reverse electron transport, increased Complex I ROS production, decreased oxygen consumption rate, and reduced the ATP/ADP ratio. Supplementation with CoQ10 reportedly restored OCR and ATP/ADP ratios and reduced ROS levels.
Why it matters
It provides an in vitro mechanistic explanation for statin-associated adverse effects, suggesting that high-dose atorvastatin damages mitochondrial bioenergetics via reverse electron transport and that CoQ10 directly mitigates this toxicity at the cellular level.
Limits
This is strictly an in vitro study performed on dermal fibroblasts rather than skeletal muscle or cardiac tissue, which are the primary sites of clinical statin-induced myopathy. The abstract notes effects occur at high concentrations, which may not reflect therapeutic in vivo plasma or tissue concentrations. No clinical outcomes, in vivo pharmacokinetics, sample sizes, or numerical data are provided in the abstract.
Cited by
- supports Statins deplete the electron transport chain and cause coenzyme Q10 deficiency.