Drug & supplement interaction

Grape + Sacubitril, Valsartan

Sacubitril, Valsartan brand name: Entresto.

Minor Interaction
Medically reviewed by · Updated September 2026
The bottom line Minor

Grape has a minor interaction with Sacubitril, Valsartan. It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grape and Sacubitril, Valsartan

Here is the interaction we found between these two, with the evidence behind it.

Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Why this applies to Sacubitril, Valsartan

Sacubitril, Valsartan falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Grape interacts with.

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version: the worry is that grape seed extract or grape juice might slow down a liver enzyme called CYP2C9, which helps clear the valsartan part of Entresto. If that happened, a bit more drug could linger in your system, which could nudge your blood pressure lower or add to side effects like dizziness, lightheadedness, or feeling tired.

But honestly, the evidence here is very thin. This is mostly based on lab dish testing, and a real-world study in healthy people found that grape juice didn't change how a similar CYP2C9 drug was cleared. The research is conflicting, and the chance of a problem is rated as unlikely. Everyday grapes in your diet are not a concern. If you're thinking about a concentrated grape seed supplement, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  2. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  3. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Grape Also Interacts With Other Medications

Grape has 868 moderate, 41 minor known drug interactions in our database — the Sacubitril, Valsartan one above is one of them. If you take anything else, check it against the full list below.

Moderate 868 Minor 41 No known interaction 1,921 (incl. Sacubitril, Valsartan)
Taking anything else?

Check Another of Your Medications Against Grape

Covers the 2,830 medications we’ve checked against Grape. Pick one to open its full report.

From our Q&A

Questions About Grape or Sacubitril, Valsartan

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grape or Sacubitril, Valsartan, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Sacubitril, Valsartan

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sacubitril, Valsartan page lists 249 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Lithium (major) and Oleander (major).

By severity: 7 major · 206 moderate · 36 minor.

From our pharmacist’s overview on the Sacubitril, Valsartan page

“Entresto (sacubitril and valsartan) is a heart failure medicine, and heart failure patients tend to be heavy supplement users, reaching for fish oil, potassium, and herbal blood-pressure remedies. That instinct carries real risk here.”

Reviewed by 2 · Jul 18, 2026

Open the Sacubitril, Valsartan interaction page

One more smart check

Taking Grape as Part of a Dietary Supplement Product? Check It for Interactions

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Sacubitril, Valsartan too, on top of Grape — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Grape and Sacubitril, Valsartan Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Grape
Top 5%

#33 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Sacubitril, Valsartan
Top 25%

#323 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Medication

About Valsartan and Sacubitril

What Is Valsartan and Sacubitril Used For?

Brand name: Entresto

Sacubitril and valsartan is used to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. The benefit is most clearly seen in patients whose heart pumps with a lower-than-normal ejection fraction (the percentage of blood the heart pushes out with each beat).

It is also approved to treat symptomatic heart failure with reduced left ventricular function in children aged 1 year and older. In pediatric patients, it lowers a blood marker of heart stress (NT-proBNP) and is expected to improve heart outcomes.

See full Valsartan and Sacubitril drug information
Keep checking

Other Drugs & Grape

Browse every other medication we’ve checked against Grape — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
868Moderate
41Minor
1,920No known interaction
868 Moderate 41 Minor 1,920 No interaction
Moderate

868 interactions

Showing 60 of 868 moderate interactions — see all 868 on the Grape page.

Minor

41 interactions

No interaction 1,920 drugs checked — show the list

We also checked Grape against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,920 medications checked with no known interaction — see the full Grape list.

See the full Grape interactions page
See every supplement checked against Sacubitril, Valsartan, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Grape monograph › Uses, safety, and every drug interaction in one place Sacubitril, Valsartan supplement interactions › Every supplement checked against Sacubitril, Valsartan, ranked by severity Valsartan and Sacubitril drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Grape and Sacubitril, Valsartan Together: Common Questions

Can you take Grape with Sacubitril, Valsartan?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Grape and Sacubitril, Valsartan interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Sacubitril, Valsartan and Grape?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.