Drug & supplement interaction

Gossypol + Sacubitril, Valsartan

Sacubitril, Valsartan brand name: Entresto.

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

Gossypol has a moderate interaction with Sacubitril, Valsartan. Theoretically, gossypol might increase the risk of hypokalemia when taken with potassium-depleting diuretic drugs.

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

Gossypol and Sacubitril, Valsartan

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

Moderate

DIURETIC DRUGS

Why this applies to Sacubitril, Valsartan

Sacubitril, Valsartan falls under DIURETIC DRUGS — the group Gossypol interacts with.

Theoretically, gossypol might increase the risk of hypokalemia when taken with potassium-depleting diuretic drugs.
Clinical research shows that gossypol has potassium-depleting effects and can cause hypokalemia. Initiation of potassium supplementation or an increase in potassium supplement dose may be necessary for some patients.
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 gist with Entresto (sacubitril/valsartan) and gossypol. Gossypol has been shown in research to lower potassium levels in the body. That matters here because heart failure patients on Entresto already get watched closely for potassium changes. If gossypol pulls your potassium too low, you could feel muscle weakness, cramping, fatigue, or even heart rhythm problems, which is the last thing you want when your heart is already working hard.

I'll be honest, this concern is mostly theoretical, based on how gossypol behaves rather than studies pairing it with Entresto. But gossypol isn't a safe or approved supplement to begin with, so please don't self-treat with it. Talk with your pharmacist or doctor before mixing anything new with your heart medicine.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Woolley, R. J. Contraception--a look forward, Part II: Mifepristone and gossypol. J.Am.Board Fam.Pract. 1991;4(2):103-113.
  2. Bushunow, P., Reidenberg, M. M., Wasenko, J., Winfield, J., Lorenzo, B., Lemke, S., Himpler, B., Corona, R., and Coyle, T. Gossypol treatment of recurrent adult malignant gliomas. J.Neurooncol. 1999;43(1):79-86. PubMed
  3. Reidenberg, M. M. Environmental inhibition of 11beta-hydroxysteroid dehydrogenase. Toxicology 4-3-2000;144(1-3):107-111.
  4. Song, D., Lorenzo, B., and Reidenberg, M. M. Inhibition of 11 beta-hydroxysteroid dehydrogenase by gossypol and bioflavonoids. J.Lab Clin.Med. 1992;120(5):792-797.
  5. Fu, Y. F., Zhang, S. L., Lu, Z. M., and Wang, W. Effects of gossypol on the activity of kidney (Na+ + K+)-ATPase and the functions of erythrocyte membrane. Contraception 1988;37(2):179-184. PubMed
  6. Fu, Y. F., Zhang, S. L., Lu, Z. M., and Wang, W. Effects of gossypol on the activity of rabbit kidney Na,K-ATPase and the functions of human erythrocyte membrane. Prog.Clin.Biol.Res. 1988;268B:385-392.
  7. Kjaergaard, N. [Male contraception]. Ugeskr.Laeger 9-8-1986;148(37):2335-2338.
  8. Bi, X. F., Ye, Y. X., Yang, H. F., and Zhang, Z. R. [Preliminary study on gossypol in causing hypokalemia (author's transl)]. Zhongguo Yi.Xue.Ke.Xue.Yuan Xue.Bao. 1981;3(3):175-178.
  9. Aitken, R. J., Liu, J., Best, F. S., and Richardson, D. W. An analysis of the direct effects of gossypol on human spermatozoa. Int.J.Androl 1983;6(2):157-167. PubMed
  10. Waites, G. M. Male fertility regulation: the challenges for the year 2000. Br.Med Bull. 1993;49(1):210-221. PubMed
  11. Reidenberg, M. M., Gu, Z. P., Lorenzo, B., Coutinho, E., Athayde, C., Frick, J., Alvarez, F., Brache, V., and Emuveyan, E. E. Differences in serum potassium concentrations in normal men in different geographic locations. Clin.Chem. 1993;39(1):72-75. DOI

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

Gossypol Also Interacts With Other Medications

Gossypol has 103 moderate 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 103 No known interaction 2,727 (incl. Sacubitril, Valsartan)
Taking anything else?

Check Another of Your Medications Against Gossypol

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

Everything else you take

See Every Supplement That Interacts With Sacubitril, Valsartan

This page covers Gossypol 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

How much people look this up

Where Gossypol 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 Gossypol
Steady interest

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

29 days ago today
Medication Sacubitril, Valsartan
Top 10%

#260 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 Gossypol

What is Gossypol?

Gossypol
  • Male contraception (research interest)
  • Reduction of sperm production
  • Endometriosis (historical/research)
  • Antiviral and antiparasitic research
  • Cancer cell research

Gossypol is a toxic yellow pigment from cotton plants that has been studied mainly as an experimental male contraceptive because it can lower sperm production. It is not an approved or safe over-the-counter supplement, and it carries serious risks including possibly permanent infertility, low potassium, and organ toxicity. It should not be used for self-treatment.

Read the full Gossypol 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 & Gossypol

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

0Major
103Moderate
0Minor
2,726No known interaction
103 Moderate 2,726 No interaction
Moderate

103 interactions

Showing 60 of 103 moderate interactions — see all 103 on the Gossypol page.

No interaction 2,726 drugs checked — show the list

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

Showing the 60 most looked-up of 2,726 medications checked with no known interaction — see the full Gossypol list.

See the full Gossypol 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
Gossypol 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 Gossypol and Sacubitril, Valsartan Together: Common Questions

Can you take Gossypol 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.
How serious is the Gossypol 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

Still Have a Question About Sacubitril, Valsartan and Gossypol?

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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.