Drug & supplement interaction

Cocoa + Aspirin, Diphenhydramine, Phenylpropanolamine

Aspirin, Diphenhydramine, Phenylpropanolamine brand name: Alka Seltzer Plus Night Time Effervescent.

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

Aspirin, Diphenhydramine, Phenylpropanolamine falls into 3 drug categories that Cocoa can interact with; the most serious is rated moderate. Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

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

Cocoa and Aspirin, Diphenhydramine, Phenylpropanolamine

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

Why Are There 3 Interactions?

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

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 3

Why this applies to Aspirin, Diphenhydramine, Phenylpropanolamine

Aspirin, Diphenhydramine, Phenylpropanolamine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Cocoa interacts with.

Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity and increase aspirin-induced bleeding time. For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation.
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

This combo product contains aspirin, which is the piece that matters here. Aspirin already thins the blood a bit by keeping platelets from clumping together. Cocoa's flavanols can do something similar, so on paper, pairing a lot of cocoa with aspirin might nudge your bleeding risk a little higher. In real life that could look like easier bruising, a nosebleed that takes a while to stop, or a small cut bleeding longer than usual.

Keep in mind this is a theoretical concern based on how the two work, not a strong red flag. A normal cup of hot cocoa or a square of chocolate is very unlikely to cause a problem. Concentrated cocoa or flavanol supplements are where I'd be more cautious. If you take aspirin daily or have a bleeding condition, just run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Dietrich R, Paglieroni TG, Wun T, et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72:30-5. PubMed
  2. Flammer AJ, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-82. PubMed
  3. Zubair, M. H., Zubair, M. H., Zubair, M. N., Zubair, M. M., Aftab, T., and Asad, F. Augmentation of anti-platelet effects of aspirin. J Pak Med.Assoc. 2011;61(3):304-307.
  4. Rein, D., Paglieroni, T. G., Wun, T., Pearson, D. A., Schmitz, H. H., Gosselin, R., and Keen, C. L. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72(1):30-35. PubMed
  5. Pearson, D. A., Paglieroni, T. G., Rein, D., Wun, T., Schramm, D. D., Wang, J. F., Holt, R. R., Gosselin, R., Schmitz, H. H., and Keen, C. L. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb.Res 5-15-2002;106(4-5):191-1 PubMed
  6. Murphy, K. J., Chronopoulos, A. K., Singh, I., Francis, M. A., Moriarty, H., Pike, M. J., Turner, A. H., Mann, N. J., and Sinclair, A. J. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr 2 PubMed
  7. Innes, A. J., Kennedy, G., McLaren, M., Bancroft, A. J., and Belch, J. J. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003;14(5):325-327. PubMed
  8. Hermann, F., Spieker, L. E., Ruschitzka, F., Sudano, I., Hermann, M., Binggeli, C., Luscher, T. F., Riesen, W., Noll, G., and Corti, R. Dark chocolate improves endothelial and platelet function. Heart 2006;92(1):119-120.
  9. Heptinstall, S., May, J., Fox, S., Kwik-Uribe, C., and Zhao, L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc.Pharmacol. 2006;47 Suppl 2:S197-S205. PubMed
  10. Hamed, M. S., Gambert, S., Bliden, K. P., Bailon, O., Singla, A., Antonino, M. J., Hamed, F., Tantry, U. S., and Gurbel, P. A. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South.Med J 2008;101(12):1203- PubMed
  11. Flammer, A. J., Sudano, I., Wolfrum, M., Thomas, R., Enseleit, F., Periat, D., Kaiser, P., Hirt, A., Hermann, M., Serafini, M., Leveques, A., Luscher, T. F., Ruschitzka, F., Noll, G., and Corti, R. Cardiovascular effects of flavanol-rich chocolate in pat
  12. Seecheran NA, Sukha D, Grimaldos K, et al. Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study. Open Heart 2022;9(2):e002066.
Moderate

STIMULANT DRUGS

2 of 3

Aspirin, Diphenhydramine, Phenylpropanolamine also falls under STIMULANT DRUGS.

Theoretically, concomitant use might increase stimulant adverse effects.
Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects.
Severity Moderate Likelihood Probable Evidence C

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

The piece to watch here is the phenylpropanolamine in this combo product. It's a decongestant-type stimulant, and cocoa naturally contains a little caffeine, which is also a mild stimulant. Stacking the two together could, in theory, nudge up stimulant-style side effects like a faster or pounding heartbeat, jitteriness, trouble sleeping, or a small rise in blood pressure.

Honestly, this concern is based on expert opinion rather than strong studies, and a normal cup of hot cocoa or a bit of chocolate isn't likely to cause trouble for most people. The amount matters more with concentrated cocoa supplements. If you have high blood pressure or heart issues, or you notice your heart racing, check in with your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
Moderate

PHENYLPROPANOLAMINE

3 of 3

Aspirin, Diphenhydramine, Phenylpropanolamine also falls under PHENYLPROPANOLAMINE.

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Cocoa contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.
Severity Moderate Likelihood Probable Evidence B

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

Here's the thing to watch with this combo product: one of its ingredients, phenylpropanolamine, is a decongestant that can tighten blood vessels and nudge your blood pressure up. Cocoa naturally contains a little caffeine, another mild stimulant, so the two together can add up and push blood pressure a bit higher. There's also a chance phenylpropanolamine slows how you clear caffeine, leaving more of it in your system, which may leave you feeling jittery, restless, or with a racing heart.

This is mostly a theoretical, additive concern, and a cup of cocoa is far less worrisome than concentrated cocoa or caffeine supplements. Still, if you have high blood pressure or heart issues, check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  2. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. 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

Cocoa Also Interacts With Other Medications

Cocoa has 634 moderate, 26 minor known drug interactions in our database — the Aspirin, Diphenhydramine, Phenylpropanolamine one above is among them. If you take anything else, check it against the full list below.

Moderate 634 Minor 26 No known interaction 2,170 (incl. Aspirin, Diphenhydramine, Phenylpropanolamine)
Taking anything else?

Check Another of Your Medications Against Cocoa

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Diphenhydramine, Phenylpropanolamine

This page covers Cocoa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Diphenhydramine, Phenylpropanolamine page lists 361 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 17 major · 308 moderate · 36 minor.

From our pharmacist’s overview on the Aspirin, Diphenhydramine, Phenylpropanolamine page

“A cold remedy used for a few nights can still collide with supplements taken daily, and Alka Seltzer Plus Night Time (aspirin, diphenhydramine, phenylpropanolamine) is one to treat with genuine care. Its three ingredients thin the blood, sedate, and stimulate all at once, which is why 361 supplements and herbs are on file here.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Diphenhydramine, Phenylpropanolamine interaction page

One more smart check

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

We hold 844 real supplement products containing Cocoa, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cocoa. Your product may carry other ingredients that interact with Aspirin, Diphenhydramine, Phenylpropanolamine too, on top of Cocoa — 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 Cocoa and Aspirin, Diphenhydramine, Phenylpropanolamine 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 Cocoa
Top 25%

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

29 days ago today
Medication Aspirin, Diphenhydramine, Phenylpropanolamine
Top 10%

#200 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 Cocoa

What is Cocoa?

Cocoa
  • Heart and blood vessel health
  • High blood pressure
  • High cholesterol
  • Mental focus and mood
  • Skin moisturizing (cocoa butter)

Cocoa is rich in plant compounds called flavanols that may modestly support blood vessel function and blood pressure, but most chocolate products are high in sugar, fat, and calories, which can offset any benefit. Enjoy cocoa as part of a balanced diet, and talk to your pharmacist before using concentrated cocoa supplements, especially if you have heart or blood pressure conditions.

Read the full Cocoa monograph & all interactions
Keep checking

Other Drugs & Cocoa

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

0Major
634Moderate
26Minor
2,169No known interaction
634 Moderate 26 Minor 2,169 No interaction
Moderate

634 interactions

Showing 60 of 634 moderate interactions — see all 634 on the Cocoa page.

Minor

26 interactions

No interaction 2,169 drugs checked — show the list

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

Showing the 60 most looked-up of 2,169 medications checked with no known interaction — see the full Cocoa list.

See the full Cocoa interactions page
See every supplement checked against Aspirin, Diphenhydramine, Phenylpropanolamine, 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
Cocoa monograph › Uses, safety, and every drug interaction in one place Aspirin, Diphenhydramine, Phenylpropanolamine supplement interactions › Every supplement checked against Aspirin, Diphenhydramine, Phenylpropanolamine, 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 Cocoa and Aspirin, Diphenhydramine, Phenylpropanolamine Together: Common Questions

Can you take Cocoa with Aspirin, Diphenhydramine, Phenylpropanolamine?
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 Cocoa and Aspirin, Diphenhydramine, Phenylpropanolamine?
Aspirin, Diphenhydramine, Phenylpropanolamine belongs to more than one drug category, and Cocoa 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 Cocoa and Aspirin, Diphenhydramine, Phenylpropanolamine 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 Aspirin, Diphenhydramine, Phenylpropanolamine and Cocoa?

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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.