Drug & supplement interaction

Soy + Sacubitril, Valsartan

Sacubitril, Valsartan brand name: Entresto.

Moderate Interaction
The bottom line Moderate

Sacubitril, Valsartan falls into 3 drug categories that Soy can interact with; the most serious is rated moderate. Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Soy and Sacubitril, Valsartan

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Soy interacts with whole categories of medication. Sacubitril, Valsartan falls into 3 of those categories, so it can interact with Soy in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIHYPERTENSIVE DRUGS

1 of 3

Why this applies to Sacubitril, Valsartan

Sacubitril, Valsartan falls under ANTIHYPERTENSIVE DRUGS — the group Soy interacts with.

Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.
Although some contradictory research exists, most clinical evidence suggests that consuming soy protein modestly reduces systolic and diastolic blood pressure in individuals with prehypertension or hypertension.
Severity Moderate Likelihood Possible Evidence A

Interaction 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.

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

Entresto already works hard to lower your blood pressure and ease the load on your heart. Soy isn't broken down by the same pathways, so this isn't about your body clearing the drug differently. Instead, it's a simple add-on effect: research suggests soy protein can modestly nudge blood pressure down on its own. Stack that on top of Entresto and your readings could dip a little lower than expected.

For most people, eating tofu, edamame, or soy milk as part of meals is unlikely to cause trouble. The bigger question is with concentrated soy supplements. If you notice dizziness, lightheadedness, feeling faint when you stand up, or unusual tiredness, mention it to your pharmacist or doctor before changing anything.

References
  1. He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: A randomized, controlled trial. Ann Intern Med 2005;143:1-9. PubMed
  2. Sacks FM, Lichtenstein A, Van Horn L, et al. Soy protein, isoflavones, and cardiovascular health. An American Heart Association Science Advisory for Professionals from the Nutrition Committee. Circulation 2006;113:1034-44. PubMed
  3. Altorf-van der Kuil, W., Engberink, M. F., Brink, E. J., van Baak, M. A., Bakker, S. J., Navis, G., van, 't, V, and Geleijnse, J. M. Dietary protein and blood pressure: a systematic review. PLoS.One. 2010;5(8):e12102. PubMed
Moderate

DIURETIC DRUGS

2 of 3

Sacubitril, Valsartan also falls under DIURETIC DRUGS.

Theoretically, soy might have additive effects when used with diuretic drugs.
Animal research suggests that genistein, a soy isoflavone, increases diuresis within 6 hours of subcutaneous administration in rats. The effects seem to be similar to those of furosemide. This effect has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the honest picture with Entresto (sacubitril/valsartan) and soy. The concern on file is that soy isoflavones, mainly genistein, might act a little like a water pill and nudge you toward losing more fluid. The catch is that this comes from a study in rats given an injection, not from people eating soy or taking soy supplements. So this is very much a theoretical idea right now.

Since Entresto already lowers blood pressure and shifts fluid balance, the worry would be a mild add-on effect, things like feeling lightheaded, dizzy, or dehydrated, especially when standing up. For most folks, normal soy foods like tofu or edamame are very unlikely to cause trouble. Concentrated isoflavone supplements are the bigger unknown, so it's worth a quick check with your pharmacist or doctor before starting one.

References
  1. Gimenez, I., Martinez, R. M., Lou, M., Mayoral, J. A., Garay, R. P., and Alda, J. O. Salidiuretic action by genistein in the isolated, perfused rat kidney. Hypertension 1998;31(2):706-711. PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Sacubitril, Valsartan also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.
In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected.
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: this is a very minor concern. The idea is that soy might slightly speed up an enzyme called CYP2C9, which helps process the valsartan part of Entresto. In theory, that could nudge blood levels of valsartan a touch lower and make it work a little less. In practice, this hasn't held up in people. When researchers gave women a soy supplement alongside losartan (a similar drug handled by the same enzyme), blood levels didn't really change.

So enjoying tofu, edamame, or soy milk shouldn't get in the way of your heart failure treatment. If you're thinking about concentrated soy isoflavone capsules, just run it by your pharmacist or doctor first so they can keep an eye on your blood pressure and how you're feeling.

References
  1. Wang G, Xiao CQ, Li Z, et al. Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. Ann Pharmacother 2009;43:1045-9. PubMed

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

Soy Also Interacts With Other Medications

Soy has 9 major, 342 moderate, 259 minor known drug interactions in our database — the Sacubitril, Valsartan one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Soy

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

Everything else you take

See Every Supplement That Interacts With Sacubitril, Valsartan

This page covers Soy 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 Soy as Part of a Dietary Supplement Product? Check It for Interactions

We hold 821 real supplement products containing Soy, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Soy. Your product may carry other ingredients that interact with Sacubitril, Valsartan too, on top of Soy — 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 Soy 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 Soy
Top 25%

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

29 days ago today
Medication Sacubitril, Valsartan
Top 25%

#428 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 Soy

What is Soy?

  • Menopause symptoms (hot flashes)
  • Heart and cholesterol health
  • Bone health
  • Plant-based protein source
  • General nutrition

Soy is a nutritious bean that is a staple food and a popular source of plant protein and isoflavones. Eating soy foods as part of a balanced diet is generally considered safe for most people, and there is moderate evidence it may modestly help cholesterol and some menopause symptoms, though results vary. Talk with your pharmacist or doctor before using concentrated soy isoflavone supplements, especially if you have a history of hormone-sensitive conditions.

Read the full Soy 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 & Soy

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

9Major
342Moderate
259Minor
2,219No known interaction
Major

9 interactions

Moderate

342 interactions

Showing 60 of 342 moderate interactions — see all 342 on the Soy page.

Minor

259 interactions

Showing 60 of 259 minor interactions — see all 259 on the Soy page.

No interaction 2,219 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Soy and Sacubitril, Valsartan Together: Common Questions

Can you take Soy with Sacubitril, Valsartan?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Soy and Sacubitril, Valsartan?
Sacubitril, Valsartan belongs to more than one drug category, and Soy interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Soy and Sacubitril, Valsartan interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

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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.