Drug & supplement interaction

L-arginine + Hydrochlorothiazide, Spironolactone

Hydrochlorothiazide, Spironolactone brand names: Spirozine, Aldactazide, Aldactide 25, Aldactide 50.

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

Hydrochlorothiazide, Spironolactone falls into 2 drug categories that L-arginine can interact with; the most serious is rated moderate. Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

L-arginine and Hydrochlorothiazide, Spironolactone

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

L-arginine interacts with whole categories of medication. Hydrochlorothiazide, Spironolactone falls into 2 of those categories, so it can interact with L-arginine in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIHYPERTENSIVE DRUGS

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Why this applies to Hydrochlorothiazide, Spironolactone

Hydrochlorothiazide, Spironolactone falls under ANTIHYPERTENSIVE DRUGS — the group L-arginine interacts with.

Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
L-arginine increases nitric oxide, which causes vasodilation. Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension. Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

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

Your combination pill (hydrochlorothiazide plus spironolactone) already works to lower blood pressure by helping your body shed extra fluid and salt. L-arginine pushes in the same direction by raising nitric oxide, which relaxes and widens your blood vessels. Stacking the two can have an additive blood-pressure-lowering effect, so your pressure could dip a little lower than expected.

In real life that might show up as dizziness, lightheadedness when you stand up, fatigue, or feeling faint. This concern is mostly theoretical and based on how these work, not strong studies, so for many people it stays mild. Still, if you take L-arginine, mention it to your pharmacist or doctor, and check your blood pressure at home so any changes get caught early.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Siani A, Pagano E, Iacone R, et al. Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens 2000;13:547-51. PubMed
  2. Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64. PubMed
  3. Huynh NT, Tayek JA. Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation. J Am Coll Nutr 2002;21:422-7.. PubMed
  4. Higashi Y, Oshima T, Sasaki S, et. al. Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension. Hypertension. 1998 Jul;32(1):16-24.
  5. Komers, R., Komersova, K., Kazdova, L., Ruzickova, J., and Pelikanova, T. Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans. J Hypertens. 2000;18(1):51-59. PubMed
  6. Nagaya, N., Uematsu, M., Oya, H., Sato, N., Sakamaki, F., Kyotani, S., Ueno, K., Nakanishi, N., Yamagishi, M., and Miyatake, K. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmona
  7. Stokes, G. S., Barin, E. S., Gilfillan, K. L., and Kaesemeyer, W. H. Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave. Am J Hypertens. 2003;16(9 Pt 1):719-724.
  8. Palloshi, A., Fragasso, G., Piatti, P., Monti, L. D., Setola, E., Valsecchi, G., Galluccio, E., Chierchia, S. L., and Margonato, A. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension,
  9. Ast, J., Jablecka, A., Bogdanski, P., Smolarek, I., Krauss, H., and Chmara, E. Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring. Med.Sci.Monit. 2
  10. Dong, J. Y., Qin, L. Q., Zhang, Z., Zhao, Y., Wang, J., Arigoni, F., and Zhang, W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am.Heart J 2011;162(6):959-965. PubMed
  11. Dell'Omo, G., Catapano, G., Ebel, M., Gazzano, A., Ducci, M., Del, Chicca M., Clerico, A., and Pedrinelli, R. [Pressor, renal and endocrine effects of systemic infusion of L-arginine in hypertensive patients]. Ann.Ital Med.Int. 1995;10(2):107-112.
  12. Higashi, Y., Oshima, T., Ozono, R., Watanabe, M., Matsuura, H., and Kajiyama, G. Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension. Hypertension 1995;25(4 Pt 2):898-902.
  13. Li H, Liu Q, Zou Z, et al. L-arginine supplementation to mitigate cardiovascular effects of walking outside in the context of traffic-related air pollution in participants with elevated blood pressure: A randomized, double-blind, placebo-controlled trial. PubMed
  14. Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei K. The Effect of L-arginine Supplementation On Blood Pressure in Adults: A Systematic Review and Dose-response Meta-analysis of Randomized Clinical Trials. Adv Nutr 2021. PubMed
Moderate

POTASSIUM-SPARING DIURETICS

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Hydrochlorothiazide, Spironolactone also falls under POTASSIUM-SPARING DIURETICS.

Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
Potassium-sparing diuretics can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in 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 thing to keep an eye on with your combo pill. The spironolactone part is a potassium-sparing diuretic, meaning it helps your body hold onto potassium rather than flush it out. The hydrochlorothiazide piece actually pushes potassium the other way, but spironolactone tends to win when it comes to raising potassium. L-arginine has, in a few cases, been linked to higher potassium levels too. So stacking them together could, in theory, nudge your potassium up more than you'd want.

To be fair, this concern is based on how these things work on paper, not on strong studies, so I don't want to alarm you. Still, if your potassium climbs too high you might feel muscle weakness, tingling, or an irregular heartbeat. It's worth a quick chat with your pharmacist or doctor, who can simply check a potassium level if needed.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hertz, P. and Richardson, J. A. Arginine-induced hyperkalemia in renal failure patients. Arch.Intern.Med. 1972;130(5):778-780. DOI
  2. Bushinsky, D. A. and Gennari, F. J. Life-threatening hyperkalemia induced by arginine. Ann.Intern.Med. 1978;89(5 Pt 1):632-634. 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

L-arginine Also Interacts With Other Medications

L-arginine has 394 moderate, 8 minor known drug interactions in our database — the Hydrochlorothiazide, Spironolactone one above is among them. If you take anything else, check it against the full list below.

Moderate 394 Minor 8 No known interaction 2,428 (incl. Hydrochlorothiazide, Spironolactone)
Taking anything else?

Check Another of Your Medications Against L-arginine

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

From our Q&A

Questions About L-arginine or Hydrochlorothiazide, Spironolactone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers L-arginine or Hydrochlorothiazide, Spironolactone, 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 Hydrochlorothiazide, Spironolactone

This page covers L-arginine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrochlorothiazide, Spironolactone page lists 235 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), Asarabacca (major) and Dolomite (major).

By severity: 10 major · 199 moderate · 26 minor.

From our pharmacist’s overview on the Hydrochlorothiazide, Spironolactone page

“Hydrochlorothiazide with spironolactone (Aldactazide) deserves genuine care around supplements, and the ten major-rated interactions on this list of 235 are the ones to understand before anything else. Most entries either add to the drug's blood-pressure-lowering effect, sometimes enough to cause dizziness or fainting, or amplify its d…”

Reviewed by 2 · Jul 18, 2026

Open the Hydrochlorothiazide, Spironolactone interaction page

One more smart check

Taking L-arginine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 26 real supplement products containing L-arginine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-arginine. Your product may carry other ingredients that interact with Hydrochlorothiazide, Spironolactone too, on top of L-arginine — 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 L-arginine and Hydrochlorothiazide, Spironolactone 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 L-arginine
Steady interest

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

29 days ago today
Medication Hydrochlorothiazide, Spironolactone
Top 25%

#395 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 L-arginine

What is L-arginine?

L-arginine
  • High blood pressure
  • Erectile dysfunction
  • Athletic performance
  • Chest pain (angina)
  • Improving blood flow

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for blood pressure, erectile dysfunction, and exercise, but the evidence is mixed and stronger for some uses than others. It is generally well tolerated in healthy adults, but talk with a pharmacist or doctor before using it, especially if you have heart problems or take other medicines.

Read the full L-arginine monograph & all interactions
Keep checking

Other Drugs & L-arginine

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

0Major
394Moderate
8Minor
2,427No known interaction
394 Moderate 8 Minor 2,427 No interaction
Moderate

394 interactions

Showing 60 of 394 moderate interactions — see all 394 on the L-arginine page.

Minor

8 interactions

No interaction 2,427 drugs checked — show the list

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

Showing the 60 most looked-up of 2,427 medications checked with no known interaction — see the full L-arginine list.

See the full L-arginine interactions page
See every supplement checked against Hydrochlorothiazide, Spironolactone, 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
L-arginine monograph › Uses, safety, and every drug interaction in one place Hydrochlorothiazide, Spironolactone supplement interactions › Every supplement checked against Hydrochlorothiazide, Spironolactone, ranked by severity 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 L-arginine and Hydrochlorothiazide, Spironolactone Together: Common Questions

Can you take L-arginine with Hydrochlorothiazide, Spironolactone?
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 2 interactions listed for L-arginine and Hydrochlorothiazide, Spironolactone?
Hydrochlorothiazide, Spironolactone belongs to more than one drug category, and L-arginine 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 L-arginine and Hydrochlorothiazide, Spironolactone 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 Hydrochlorothiazide, Spironolactone and L-arginine?

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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.