Grapefruit Juice and Simvastatin: what the research found
PubMed indexes 8 records that name Grapefruit Juice and Simvastatin together, either in the title or in an interaction, co-administration, or pharmacokinetic context. The key findings come first, in the authors’ own words, followed by every study with its design and PubMed link.
A summary of published research, not medical advice. A pharmacist can check any combination against your full list of medicines and supplements.
Reviews and human studies first. Each quote is the authors’ own conclusion about their study, not a NutriStack assessment, and a single study is not a consensus.
“Even one glass of grapefruit juice, taken daily, considerably increases the plasma concentrations of simvastatin and simvastatin acid. Grapefruit juice may increase both the cholesterol-lowering effect and the risk of adverse effects of simvastatin.”
“When simvastatin is taken 24 hours after ingestion of "high-dose" grapefruit juice, the effect of grapefruit juice on the AUC of simvastatin is only about 10% of the effect observed during concomitant intake of grapefruit juice and simvastatin. The interaction potential of even high amounts of grapefruit juice with CYP3A4 substrates dissipates within 3 to 7 days after ingestion of the last dose of grapefruit juice.”
“Grapefruit juice greatly increased serum concentrations of simvastatin and simvastatin acid and, to a lesser extent, those of active and total HMG-CoA reductase inhibitors. The probable mechanism of this interaction was inhibition of CYP3A4-mediated first-pass metabolism of simvastatin by grapefruit juice in the small intestine.”
The research
8 studies naming Grapefruit Juice and Simvastatin.
Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.
British journal of clinical pharmacology · 2004 · PMID 15206993
Clinical TrialRandomized Controlled Trial
“Even one glass of grapefruit juice, taken daily, considerably increases the plasma concentrations of simvastatin and simvastatin acid. Grapefruit juice may increase both the cholesterol-lowering effect and the risk of adverse effects of simvastatin.”
Names both Grapefruit Juice and Simvastatin in its title.
Clinical pharmacology and therapeutics · 2000 · PMID 11061578
Clinical TrialControlled Clinical Trial
“When simvastatin is taken 24 hours after ingestion of "high-dose" grapefruit juice, the effect of grapefruit juice on the AUC of simvastatin is only about 10% of the effect observed during concomitant intake of grapefruit juice and simvastatin. The interaction potential of even high amounts of grapefruit juice with CYP3A4 substrates dissipates within 3 to 7 days after ingestion of the last dose of grapefruit juice.”
Names both Grapefruit Juice and Simvastatin in its title.
“Grapefruit juice greatly increased serum concentrations of simvastatin and simvastatin acid and, to a lesser extent, those of active and total HMG-CoA reductase inhibitors. The probable mechanism of this interaction was inhibition of CYP3A4-mediated first-pass metabolism of simvastatin by grapefruit juice in the small intestine.”
Names both Grapefruit Juice and Simvastatin in its title.
Research Support, U.S. Gov't, Non-P.H.S.Animal study
“Interestingly, treatment with RS- or DS-GFJ alone significantly decreased plasma cholesterol levels by 22 % and 30 %, respectively. In conclusion, our results suggest that toxic effects in rats of concomitant intake of simvastatin and GFJ over 28 days are not more pronounced than those of simvastatin alone and that dose relationships between the administration of the juice and the drug may be important in determining the magnitude of the interaction.”
Names both Grapefruit Juice and Simvastatin in its title.
Clinical pharmacology and therapeutics · 1999 · PMID 10460065
Clinical TrialRandomized Controlled Trial
“Grapefruit juice significantly increased serum concentrations of atorvastatin acid, atorvastatin lactone, and active and total HMG-CoA reductase inhibitors, probably by decreasing CYP3A4-mediated first-pass metabolism of atorvastatin in the small intestine. On the other hand, grapefruit juice had no effect on the pharmacokinetics of pravastatin.”
Names Grapefruit Juice and Simvastatin together in an interaction, co-administration, or pharmacokinetic context.
Clinical pharmacology and therapeutics · 1998 · PMID 9585793
Clinical TrialRandomized Controlled Trial
“Grapefruit juice can greatly increase serum concentrations of lovastatin and its active metabolite, lovastatin acid, probably by preventing CYP3A4-mediated first-pass metabolism in the small intestine. The concomitant use of grapefruit juice with lovastatin and simvastatin should be avoided, or the dose of these 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors should be reduced accordingly.”
Names Grapefruit Juice and Simvastatin together in an interaction, co-administration, or pharmacokinetic context.
Limitations
What this evidence cannot tell you.
Search-based evidence indexes have real limits, and it is worth being explicit about them:
Selection. These records were found by searching PubMed titles and abstracts for both substance names alongside interaction and pharmacokinetic terms. Relevant work that phrases things differently, or is not indexed in PubMed, will be missing.
No effect size. The quoted conclusions are the authors’ words about their own study. We have not extracted effect direction or magnitude, and a single study’s conclusion is not a consensus.
Population mismatch. Findings in healthy volunteers, animals, or a specific patient group may not transfer to you, your dose, or your formulation.
Absence is not safety. Few published studies means the combination is under-studied, which is not the same as established as safe.
How to read this page
A literature summary, not guidance.
A study listed here is not proof that Grapefruit Juice and Simvastatin interact. Two substances can be named together in a paper that never tested them in combination, and a source listed as background may cover only one of them.
Findings are quoted from each abstract as the authors wrote them. NutriStack has not re-analysed, pooled, or reconciled them, and they may disagree with each other.
Decisions about prescription medication and supplements belong with your prescriber or pharmacist, who can see your full regimen. Our timing guide and forms guide explain the general mechanisms.
Nearby evidence
Other pairs with published research.
Pages covering Grapefruit Juice or Simvastatin alongside a different substance.
NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers Grapefruit Juice, Simvastatin, and several hundred other substances.
Log your routine, get reminders at the times you choose, and scan a label to add a product. The checker is a research and organisation tool, not a clinical decision aid.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.