Simvastatin
Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Simvastatin is a moderate-to-high intensity statin with landmark evidence from the 4S and HPS trials demonstrating significant cardiovascular mortality reduction. It is administered as an inactive lactone prodrug that is converted to the active hydroxy acid form in the liver.
Exploratory record, not a reviewed medical publication.
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What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
Simvastatin is a moderate-to-high intensity statin with landmark evidence from the 4S and HPS trials demonstrating significant cardiovascular mortality reduction. NutriStack rates the supporting evidence as strong. Common adult dosing is 10–40 mg once daily in the evening (as prescribed by your physician), though a prescriber sets the actual dose. With long-term use it can deplete coq10. This profile indexes 11 sources.
The bottom line
Evidence rating strong. Most-documented uses: lowers ldl cholesterol by 27–41% (up to 47% at the restricted 80 mg dose), reduces total mortality in patients with coronary heart disease, reduces risk of major coronary events and stroke. 11 sources indexed (2014–2025), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Prodrug hydrolyzed to the active beta-hydroxyacid form, which competitively inhibits HMG-CoA reductase. Reduces hepatic cholesterol synthesis, upregulates LDL receptor expression, and increases clearance of circulating LDL particles. Metabolized primarily by CYP3A4.
Dosing & protocol.
Should be taken in the evening because hepatic cholesterol synthesis is greatest at night; avoid large quantities of grapefruit juice3,7
What it depletes.
Nutrients this medication can lower over time, and what to replace.
CoQ10
ModerateHMG-CoA reductase inhibition reduces mevalonate pathway flux, lowering endogenous CoQ10 synthesis alongside cholesterol synthesis.
Full safety detail.
Side effects
- Myalgia and muscle pain
- Elevated liver transaminases
- Gastrointestinal disturbances
- Headache
- Rhabdomyolysis (risk increases with 80 mg dose)
- New-onset diabetes
Contraindications
- Active liver disease or unexplained persistent transaminase elevations7,8
- Pregnancy and breastfeeding
- Concurrent use of strong CYP3A4 inhibitors (itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors)
- Concurrent gemfibrozil or danazol use
- 80 mg dose restricted to patients already tolerating it for 12+ months3,7
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
5- 1Simvastatin is Efficacious in Treating Cirrhosis: A Meta-analysisPMIDZhang H, Zhang Q, Li S, Xie B · Journal of Clinical Gastroenterology · 2022
Simvastatin treatment in cirrhotic patients was associated with improved survival and reduced hepatic decompensation events
- 2Calcium Phosphate Carrying Simvastatin Enhances Bone Regeneration: A Systematic ReviewPMIDCruz R, Pesce G, Calasans-Maia J et al. · Brazilian dental journal · 2020
Cruz R, Pesce G, Calasans-Maia J et al.. Calcium Phosphate Carrying Simvastatin Enhances Bone Regeneration: A Systematic Review. Brazilian dental journal. 2020
- 3Statin use and risk of new-onset diabetes: A meta-analysis of observational studiesPMIDCasula M, Mozzanica F, Scotti L, Tragni E et al. · Nutrition, Metabolism, and Cardiovascular Diseases · 2017
Statin use was associated with a modest but statistically significant increase in risk of new-onset diabetes (approximately 9-12% increased risk), with higher risk at higher doses
- 4Systematic review of red yeast rice compared with simvastatin in dyslipidaemiaPMIDOng YC, Aziz Z · Journal of clinical pharmacy and therapeutics · 2016
Ong YC, Aziz Z. Systematic review of red yeast rice compared with simvastatin in dyslipidaemia. Journal of clinical pharmacy and therapeutics. 2016
- 5Efficacy and safety of pitavastatin versus simvastatin: a meta-analysis of randomized controlled trialsPMIDJiang Z, Gong RR, Qiu L et al. · Clinical drug investigation · 2014
Jiang Z, Gong RR, Qiu L et al.. Efficacy and safety of pitavastatin versus simvastatin: a meta-analysis of randomized controlled trials. Clinical drug investigation. 2014
Randomized controlled trials
2- 6Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trialPMIDAlvarado-Tapias E, Brujats A, Puente A et al. · Hepatology (Baltimore, Md.) · 2025
Alvarado-Tapias E, Brujats A, Puente A et al.. Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial. Hepatology (Baltimore, Md.). 2025
- 7Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trialPMIDPose E, Napoleone L, Amin A et al. · The lancet. Gastroenterology & hepatology · 2020
Pose E, Napoleone L, Amin A et al.. Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. The lancet. Gastroenterology & hepatology. 2020
Reference material
4- 8Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the 4S study. Lancet. 1994.Source linkedPMID
- 9Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals. Lancet. 2002.Source linkedPMID
- 10Li W et al. A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases. Cardiovasc Ther. 2025.Source linkedPMID
- 11Pedersen TR, Tobert JA. Simvastatin: a review. Expert opinion on pharmacotherapy. 2004Source linkedPMID
Common questions.
Quick answers about Simvastatin, drawn from the data on this page.
What is Simvastatin?
Simvastatin is a moderate-to-high intensity statin with landmark evidence from the 4S and HPS trials demonstrating significant cardiovascular mortality reduction. It is administered as an inactive lactone prodrug that is converted to the active hydroxy acid form in the liver.
What is Simvastatin used for?
Commonly cited benefits of Simvastatin include: Lowers LDL cholesterol by 27–41% (up to 47% at the restricted 80 mg dose); Reduces total mortality in patients with coronary heart disease; Reduces risk of major coronary events and stroke; Well-established long-term safety profile. NutriStack rates the overall evidence as strong.
What is a typical dose of Simvastatin?
A typical adult dose of Simvastatin is 10–40 mg once daily in the evening (as prescribed by your physician). The commonly recommended form is Oral tablet, taken in the evening. These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Simvastatin?
Reported side effects include myalgia and muscle pain, elevated liver transaminases, gastrointestinal disturbances, headache, rhabdomyolysis (risk increases with 80 mg dose), new-onset diabetes. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Simvastatin?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
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