Herb & supplement monograph

Caffeine Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by ·Updated July 2026
What is this page for?

First and foremost: how Caffeine interacts with medications. The heart of this page is the interaction list — every drug Caffeine is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Caffeine is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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Caffeine Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Caffeine drug interaction is low for most people, though a small group of medications deserves real caution. Only a small handful of interactions are rated major, and most of the rest are moderate concerns supported mainly by theoretical or animal evidence rather than proven harm in humans.

Interactions deserving the most attention

The clearest danger is combining caffeine with ephedrine, which has been linked to serious harm including high blood pressure, heart attack, stroke, and seizures. Caffeine may also raise clozapine levels and worsen its side effects, and suddenly cutting back on caffeine has raised lithium levels in case reports. Some medicines, including cimetidine, fluvoxamine, and quinolone antibiotics, slow the body's clearance of caffeine, so effects like jitteriness can build up, and caffeine can interfere with heart stress-test drugs such as dipyridamole and adenosine.

What the rest of the list means

Most other entries describe what could happen in theory, often because caffeine may affect an enzyme the body uses to process certain medications. Many come from lab or animal research, and several predicted effects have not caused meaningful problems in people, so a long list does not mean every combination is harmful.

Check your medications against Caffeine

Based on HelloPharmacist’s Caffeine interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Caffeine

655 medications have a known interaction with Caffeine, graded by severity. Select any drug for the full evidence-based detail.

8 major interactions. These combinations can be clinically significant — best avoided, or used only with close professional supervision. Always check with your pharmacist before combining them with Caffeine.

2,830 drugs
Aminophylline, Amobarbital, EphedrineAmesec
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Aminophylline, Amobarbital, Ephedrine interaction
Carbetapentane Tannate, Chlorpheniramine Tannate, Ephedrine Tannate, Phenylephrine TannateQuadratuss, Ry Tuss, Rynatuss, Tri Tannate Plus
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Carbetapentane Tannate, Chlorpheniramine Tannate, Ephedrine Tannate, Phenylephrine Tannate interaction
Dyphylline, Ephedrine, Guaifenesin, PhenobarbitalLufyllin-EPG
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Dyphylline, Ephedrine, Guaifenesin, Phenobarbital interaction
Ephedrine, Guaifenesin (otc Drug)Ephedrine Formula 400, Ephedrine Plus Tabs
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Ephedrine, Guaifenesin (otc Drug) interaction
Ephedrine, Guaifenesin, Phenobarbital, TheophyllineMudrane GG
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Ephedrine, Guaifenesin, Phenobarbital, Theophylline interaction
Ephedrine, Hydroxyzine, TheophyllineAmi Rax, Marax
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Ephedrine, Hydroxyzine, Theophylline interaction
Ephedrine, Phenobarbital, Potassium Iodide, TheophyllineMudrane, Quadrinal
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Ephedrine, Phenobarbital, Potassium Iodide, Theophylline interaction
Ephedrine, Phenobarbital, TheophyllineTedral
Major Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Read the full Caffeine + Ephedrine, Phenobarbital, Theophylline interaction
AbciximabReoPro
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Caffeine + Abciximab interaction
AbrocitinibCibinqo
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Caffeine + Abrocitinib interaction Abrocitinib drug page: uses, dosage & side effects
AcenocoumarolSintrom
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Caffeine + Acenocoumarol interaction
Acetaminophen, AspirinGemnisyn
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Caffeine + Acetaminophen, Aspirin interaction
Acetaminophen, Aspirin, CaffeineExcedrin, Excedrin Extra Strength, Excedrin Migraine
Moderate Anticoagulant/antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full Caffeine + Acetaminophen, Aspirin, Caffeine interaction
Acetaminophen, Brompheniramine, PhenylpropanolamineDimetapp Cold and Flu
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Brompheniramine, Phenylpropanolamine interaction
Acetaminophen, Butalbital, CaffeineEsgic, Esgic Plus, Fiogesic, Fioricet, Repan, Tecnal +1 more
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Butalbital, Caffeine interaction Acetaminophen, Butalbital, Caffeine drug page: uses, dosage & side effects
Acetaminophen, Butalbital, Caffeine, CodeineEsgic with Codeine, Fioricet w/ Codeine
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Butalbital, Caffeine, Codeine interaction
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, PhenylephrineHycomine Compound
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction
Acetaminophen, Caffeine, CodeineGesic C15, Gesic C30, Gesic C8, Lenoltec 1, Lenoltec 2, Lenoltec 3 +1 more
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Codeine interaction
Acetaminophen, Caffeine, Codeine, SalicylamideCodalan No.1, Codalan No.2, Codalan No.3
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Codeine, Salicylamide interaction
Acetaminophen, Caffeine, DihydrocodeineDHC Plus, Panlor DC, Panlor SS
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Dihydrocodeine interaction
Acetaminophen, Caffeine, IsomethepteneMigralam
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Isometheptene interaction
Acetaminophen, Caffeine, PyrilamineMidol Max Strength Menstrual
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Caffeine, Pyrilamine interaction
Acetaminophen, Chlorpheniramine, Codeine, PhenylephrineColrex
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PhenylpropanolamineMulti Symptom Cold Relief
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PseudoephedrineChildren's Tylenol Cold Plus Cough, Tylenol Cold Ex Strength
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction
Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, SalicylamideRhinogesic GG
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, Salicylamide interaction
Acetaminophen, Chlorpheniramine, PhenylephrineAlka-Seltzer PLUS, Histex SR, Protid
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Phenylephrine interaction
Acetaminophen, Chlorpheniramine, Phenylephrine, SalicylamideRhinogesic, Rhinogesic JR
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Phenylephrine, Salicylamide interaction
Acetaminophen, Chlorpheniramine, PhenylpropanolamineAlumadrine, Conex, Sinadrin Max Strength, Sinulin
Moderate Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Phenylpropanolamine interaction
Acetaminophen, Chlorpheniramine, Phenylpropanolamine, OpiumHista-Derfule
Moderate Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.

Read the full Caffeine + Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium interaction
Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

  • Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
  • Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
  • Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
  • No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

  • Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
  • Probable. 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.
  • Possible. 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
  • Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

  • Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
  • Each drug listed above links to the full report for that exact Caffeine combination — clinical detail, likelihood, evidence level, and citations.
  • Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
The big picture

The kinds of drugs Caffeine affects

Every type of medication (drug category) Caffeine is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 41 drug categories Caffeine interacts with
EphedrineAdenosine (adenocard)Anticoagulant/antiplatelet DrugsBeta-adrenergic AgonistsCarbamazepine (tegretol)Cimetidine (tagamet)Clozapine (clozaril)Dipyridamole (persantine)Disulfiram (antabuse)Diuretic DrugsEstrogensEthosuximide (zarontin)Felbamate (felbatol)Flutamide (eulexin)Fluvoxamine (luvox)LithiumMonoamine Oxidase Inhibitors (maois)NicotinePentobarbital (nembutal)Phenobarbital (luminal)PhenylpropanolaminePhenytoin (dilantin)Pioglitazone (actos)Quinolone AntibioticsRiluzole (rilutek)Stimulant DrugsTheophyllineValproateVerapamil (calan, Others)Alcohol (ethanol)Antidiabetes DrugsContraceptive DrugsCytochrome P450 1a2 (cyp1a2) InhibitorsFluconazole (diflucan)Metformin (glucophage)Methoxsalen (oxsoralen)Mexiletine (mexitil)PhenothiazinesTerbinafine (lamisil)Tiagabine (gabitril)Ticlopidine (ticlid)
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.

Likelihood Probable Evidence D
Adenosine (Adenocard)

Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans. However, other research shows that caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Caffeine is reported to have antiplatelet activity. Theoretically, it might increase the risk of bleeding when used concomitantly with these agents; however, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
Cimetidine decreases the rate of caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine. In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily.

Likelihood Possible Evidence B
Dipyridamole (Persantine)

Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Caffeine inhibits dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
Disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Likelihood Possible Evidence D
Estrogens

Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Flutamide (Eulexin)

Theoretically, caffeine might increase the levels and adverse effects of flutamide.
In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. However, this effect has not been reported in humans.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Lithium

Abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
Caffeine has diuretic activity. When abruptly discontinued, caffeine may alter the clearance of lithium. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal and 6 case reports of elevated serum lithium levels after reducing or eliminating caffeine intake. In one case, a male with schizoaffective disorder stabilized on lithium had an elevated lithium level after reducing his caffeine intake by 87%. At a later date, he increased his caffeine intake by 6-fold, resulting in a subtherapeutic lithium level and a recurrence of psychiatric symptoms.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies. Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis. In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension. Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

Likelihood Possible Evidence D
Nicotine

Theoretically, concomitant use might increase the risk of hypertension.
Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly.

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

Theoretically, caffeine might decrease the effects of pentobarbital.
Caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin. The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Pioglitazone (Actos)

Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2) enzyme.

Likelihood Probable Evidence B
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects.

Likelihood Probable Evidence C
Theophylline

Theoretically, caffeine might increase the levels and adverse effects of theophylline.
Large amounts of caffeine might inhibit theophylline metabolism.

Likelihood Probable Evidence C
Valproate

Theoretically, caffeine might reduce the effects of valproate and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of valproate. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Verapamil (Calan, Others)

Theoretically, verapamil might increase the levels and adverse effects of caffeine.
Verapamil increases plasma caffeine concentrations by 25%.

Likelihood Possible Evidence D
Alcohol (Ethanol)

Theoretically, concomitant use might increase levels and adverse effects of caffeine.
Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking caffeine with antidiabetes drugs might interfere with blood glucose control.
Data are conflicting. Reports claim that caffeine might increase or decrease blood sugar.

Likelihood Unlikely Evidence B
Contraceptive Drugs

Theoretically, contraceptive drugs might increase the levels and adverse effects of caffeine.
Oral contraceptives decrease the rate of caffeine clearance by 40-65%.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Inhibitors

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Caffeine is metabolized by CYP1A2. Theoretically, drugs that inhibit CYP1A2 may decrease the rate of caffeine clearance and increase caffeine levels.

Likelihood Possible Evidence D
Fluconazole (Diflucan)

Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Fluconazole decreases caffeine clearance by approximately 25%.

Likelihood Possible Evidence B
Metformin (Glucophage)

Theoretically, metformin might increase the levels and adverse effects of caffeine.
Animal research suggests that metformin can reduce caffeine metabolism. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Methoxsalen (Oxsoralen)

Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Methoxsalen reduces caffeine metabolism.

Likelihood Possible Evidence B
Mexiletine (Mexitil)

Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Mexiletine reduces caffeine metabolism.

Likelihood Possible Evidence B
Phenothiazines

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Phenothiazines, including perazine, chlorpromazine, levomepromazine, and thioridazine, can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2).

Likelihood Possible Evidence D
Terbinafine (Lamisil)

Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Terbinafine decreases the clearance of intravenous caffeine by 19%.

Likelihood Possible Evidence B
Tiagabine (Gabitril)

Theoretically, caffeine might increase the levels and adverse effects of tiagabine.
Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine.

Likelihood Possible Evidence D
Ticlopidine (Ticlid)

Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Monograph

Caffeine: Uses, Safety & Side Effects

Medically reviewed by · Reviewed July 2026 ·
The bottom line

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Part used
Seeds, leaves, and beans of various plants (e.g., coffee, tea, cacao, guarana, kola)
Common forms
Coffee, tea, energy drinks, sodas, tablets, capsules, pre-workout powders, gum
People commonly use it for
  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance
OverallUse caution

Generally safe in moderate amounts for healthy adults, but high doses can cause serious side effects.

PregnancyPossibly Safe

When used orally in amounts commonly found in foods. Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, bu...

Read the full pregnancy detail
BreastfeedingPossibly Safe

When used orally in amounts commonly found in foods. Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk c...

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Jump to a section

Overview

Caffeine is a natural stimulant that affects the brain and nervous system. It is one of the most widely used substances in the world. People take it every day, often without thinking about it, in coffee, tea, soft drinks, energy drinks, and chocolate.

Caffeine occurs naturally in the seeds, leaves, and fruit of many plants, including coffee beans, tea leaves, cacao (chocolate), guarana, and the kola nut. It can also be made in a lab and added to foods, drinks, and supplements like pre-workout powders and weight-loss products.

People most commonly use caffeine to feel more awake, fight tiredness, and improve focus. It is also added to some pain relievers and is used by athletes to help with performance.

How it works

Caffeine mainly works by blocking a chemical in the brain called adenosine. Adenosine builds up while you are awake and makes you feel sleepy. By blocking it, caffeine helps you feel more alert and less tired.

Caffeine can also slightly raise levels of certain brain chemicals and stress hormones, which is why it may make your heart beat faster and increase your energy or feeling of alertness.

These effects start within minutes and usually peak within about an hour. Caffeine stays in the body for several hours, which is why drinking it late in the day can make it harder to fall asleep.

Effectiveness

Does Caffeine work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by .

Evidence overview · 38 uses evaluated
2 Effective 2 Likely effective 5 Possibly effective 2 Leans ineffective 27 Insufficient evidence
How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.
2Likely EffectiveGood evidence, though not yet conclusive.
3Possibly EffectiveSome evidence suggests a benefit.
4Possibly IneffectiveSome evidence it may not help.
5Likely IneffectiveFairly strong evidence it doesn’t help.
6IneffectiveStrong evidence it doesn’t work.
7Insufficient Reliable Evidence to RateToo little research to say either way.
Effective Neonatal apnea
Rating & evidence shown verbatim from Natural Medicines

Oral or intravenous caffeine citrate is approved by the US Food and Drug Administration (FDA) for the short-term treatment of neonatal apnea in very preterm infants.

Effective Postoperative headache
Rating & evidence shown verbatim from Natural Medicines

Oral or intravenous caffeine is approved by the US Food and Drug Administration (FDA) for preventing headache in postoperative patients who regularly consume caffeinated products.

Likely Effective Athletic performance
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine taken as a single dose of at least 2-3 mg/kg can modestly improve endurance, muscle strength, power output, and overall athletic performance when taken prior to certain forms of athletic activity or exercise. However, the magnitude and duration of effect is variable and may be dependent on the form and dose of caffeine, as well as various individual- and activity-specific factors. Caffeine intake in excess of 800 mg daily can result in blood levels greater than those allowed by the National Collegiate Athletic Association.

Likely Effective Mental alertness
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine increases mental alertness. However, it might not improve performance or accuracy to the same extent achieved through adequate sleep.

Possibly Effective Bronchopulmonary dysplasia
Rating & evidence shown verbatim from Natural Medicines

Intravenous caffeine may reduce the risk for bronchopulmonary dysplasia in preterm infants.

Possibly Effective Diabetes
Rating & evidence shown verbatim from Natural Medicines

Dietary caffeine seems to be beneficial for the prevention of type 2 diabetes; it is unclear if it is beneficial for the prevention of gestational diabetes. Also, it is unclear if oral caffeine is beneficial in patients with type 1 or type 2 diabetes.

Possibly Effective Memory
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine seems to be beneficial for short-term memory recall in college students and extroverted personalities. It is unclear if oral caffeine is beneficial for introverted personalities or other populations.

Possibly Effective Obesity
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine, when taken in combination with ephedrine or as a component of green tea, seems to be beneficial for weight loss, short-term.

Possibly Effective Postdural puncture headache
Rating & evidence shown verbatim from Natural Medicines

Oral or intravenous caffeine seem to be beneficial for preventing postdural puncture headache.

Possibly Ineffective Atrial fibrillation
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine does not seem to prevent atrial fibrillation after cardiopulmonary bypass. In addition, it might increase the risk of gastrointestinal side effects.

Possibly Ineffective Attention deficit-hyperactivity disorder (ADHD)
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine does not seem to reduce symptoms of ADHD in children.

Also studied for 27 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Age-related cognitive decline
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine prevents cognitive decline with aging.

Insufficient Reliable Evidence To Rate Alzheimer disease
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for preventing dementia; the available research is conflicting.

Insufficient Reliable Evidence To Rate Asthma
Rating & evidence shown verbatim from Natural Medicines

Oral caffeine seems to modestly improve airway function for up to 4 hours in patients with mild to moderate asthma. However, it is unclear if oral caffeine has a clinically significant effect on asthma symptoms or quality of life.

Insufficient Reliable Evidence To Rate Cancer pain
Rating & evidence shown verbatim from Natural Medicines

It is unclear if intravenous caffeine is beneficial for cancer pain.

Insufficient Reliable Evidence To Rate Cognitive function
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine improves cognitive performance in trained athletes.

Insufficient Reliable Evidence To Rate Dementia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for preventing dementia or improving behavior in patients with dementia.

Insufficient Reliable Evidence To Rate Depression
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for depression prevention.

Insufficient Reliable Evidence To Rate Electroconvulsive therapy (ECT) augmentation
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using intravenous caffeine sodium benzoate to augment electroconvulsive therapy, there is insufficient reliable information about the clinical effects of caffeine for this condition.

Insufficient Reliable Evidence To Rate Exercise-induced hypoxemia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for hypoxemia associated with exercise.

Insufficient Reliable Evidence To Rate Exercise-induced muscle soreness
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for reducing muscle soreness during exercise.

Insufficient Reliable Evidence To Rate Gallbladder disease
Rating & evidence shown verbatim from Natural Medicines

It is unclear if increased dietary caffeine intake reduces the risk of developing gallstones.

Insufficient Reliable Evidence To Rate Hepatitis C
Rating & evidence shown verbatim from Natural Medicines

It is unclear if increased dietary caffeine reduces the risk for hepatitis C-associated severe liver inflammation, although it may reduce the risk of developing advanced fibrosis.

Insufficient Reliable Evidence To Rate Hypnic headache
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine reduces the pain associated with this rare condition.

Insufficient Reliable Evidence To Rate Hypotension
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial in people with low blood pressure.

Insufficient Reliable Evidence To Rate Intermittent claudication
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for intermittent claudication.

Insufficient Reliable Evidence To Rate Liver disease
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for liver disease prevention.

Insufficient Reliable Evidence To Rate Multiple sclerosis (MS)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for the symptoms of multiple sclerosis (MS).

Insufficient Reliable Evidence To Rate Narcolepsy
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for narcolepsy.

Insufficient Reliable Evidence To Rate Neonatal resuscitation
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine improves the likelihood for successful extubation in preterm infants.

Insufficient Reliable Evidence To Rate Nocturnal enuresis
Rating & evidence shown verbatim from Natural Medicines

Reducing caffeine intake might reduce the frequency of nocturnal enuresis episodes in children.

Insufficient Reliable Evidence To Rate Nonmelanoma skin cancer
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for nonmelanoma skin cancer prevention.

Insufficient Reliable Evidence To Rate Parkinson disease
Rating & evidence shown verbatim from Natural Medicines

Although consuming caffeinated beverages might reduce the risk of developing Parkinson disease, it is unclear if oral caffeine is beneficial for improving symptoms. Also, oral caffeine does not seem to prevent tardive dyskinesia.

Insufficient Reliable Evidence To Rate Postoperative ileus
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for improving bowel recovery following colorectal surgery. Research is conflicting and may vary depending on the type of procedure performed.

Insufficient Reliable Evidence To Rate Postoperative pain
Rating & evidence shown verbatim from Natural Medicines

It is unclear if intravenous caffeine is beneficial for reducing opioid consumption in adults undergoing surgery.

Insufficient Reliable Evidence To Rate Pre-eclampsia
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine intake affects the risk of gestational hypertension or pre-eclampsia.

Insufficient Reliable Evidence To Rate Stroke
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial for stroke prevention.

Insufficient Reliable Evidence To Rate Tinnitus
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral caffeine is beneficial in patients with chronic tinnitus.

Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.

Safety & precautions

For most healthy adults, caffeine in moderate amounts is generally considered safe. However, how people react can vary a lot. Some people are very sensitive and feel jittery or anxious from even small amounts.

Be cautious if you: have heart problems, high blood pressure, an irregular heartbeat, anxiety, panic attacks, trouble sleeping, stomach ulcers, or seizure disorders. Children and teens should limit caffeine.

Pregnancy: Caffeine crosses the placenta. High intake has been linked in some studies to risks such as miscarriage or low birth weight. Many experts advise pregnant women to limit caffeine; talk to your doctor about a safe amount for you.

Breastfeeding: Caffeine passes into breast milk in small amounts. Moderate intake is usually considered acceptable, but large amounts may make a baby fussy or have trouble sleeping. Keep your intake low and watch your baby's reaction.

Very high doses of caffeine, especially from concentrated powders or pills, can be dangerous and even life-threatening. Pure or highly concentrated caffeine powders are especially risky because it is easy to take too much by accident.

Side effects

Common side effects, especially at higher amounts, include:

  • Feeling jittery, nervous, or anxious
  • Racing or pounding heartbeat
  • Trouble sleeping
  • Upset stomach or heartburn
  • Headache
  • Needing to urinate more often
  • Shakiness or restlessness

Regular caffeine users who suddenly stop may get withdrawal symptoms such as headache, tiredness, and irritability for a few days.

Serious effects are rare but can happen with very high doses. These include a dangerously fast or irregular heartbeat, vomiting, confusion, seizures, and in extreme cases death. If you suspect a caffeine overdose, seek emergency care right away.

Caffeine: Reported Adverse Effects

Documented safety reports on Caffeine from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.

Caffeine in moderate doses is typically well tolerated.

Most Common Adverse Effects:

Orally: Anxiety, dependence with chronic use, diarrhea, diuresis, gastric irritation, headache, insomnia, muscular tremors, nausea, and restlessness.

Serious Adverse Effects (Rare):

Orally: Stroke has been reported rarely.

Reports by condition
Allergic rhinitis (hay fever) Immunologic

Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare.

  1. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2.
Anxiety Neurologic/CNS

Caffeine can cause headaches, anxiety, jitteriness, restlessness, and nervousness. In adolescents, there is an inverse correlation between the consumption of caffeine and various measurements of cognitive function. Insomnia is a frequent adverse effect in children. Caffeine may result in insomnia and sleep disturbances in adults as well. Additionally, caffeine may exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS). Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine. Finally, epidemiological research suggests that consuming more than 190 mg of caffeine daily is associated with an earlier onset of Huntington disease by 3.6 years.

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  2. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
  3. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3
  4. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216.
  5. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431.
  6. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535.
  7. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293.
  8. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092.
  9. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40.
  10. Zhang H, Lee ZX, Qiu A. Caffeine intake and cognitive functions in children. Psychopharmacology (Berl). 2020;237(10):3109-3116.
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  12. Karacan, I., Thornby, J. I., Anch, M., Booth, G. H., Williams, R. L., and Salis, P. J. Dose-related sleep disturbances induced by coffee and caffeine. Clin Pharmacol Ther 1976;20(6):682-689.
  13. Shirlow, M. J. and Mathers, C. D. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int.J.Epidemiol. 1985;14(2):239-248.
  14. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775.
  15. Brown, S. L., Salive, M. E., Pahor, M., Foley, D. J., Corti, M. C., Langlois, J. A., Wallace, R. B., and Harris, T. B. Occult caffeine as a source of sleep problems in an older population. J.Am.Geriatr.Soc. 1995;43(8):860-864.
  16. Pollak, C. P. and Bright, D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics 2003;111(1):42-46.
  17. Sin, C. W., Ho, J. S., and Chung, J. W. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009;18(1):13-21.
  18. Calamaro, C. J., Mason, T. B., and Ratcliffe, S. J. Adolescents living the 24/7 lifestyle: effects of caffeine and technology on sleep duration and daytime functioning. Pediatrics 2009;123(6):e1005-e1010.
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  20. Montandon, G., Horner, R. L., Kinkead, R., and Bairam, A. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats. J Physiol 11-15-2009;587(Pt 22):5493-5507.
  21. Skinner, T. L., Jenkins, D. G., Coombes, J. S., Taaffe, D. R., and Leveritt, M. D. Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc. 2010;42(3):571-576.
  22. Brick, C. A., Seely, D. L., and Palermo, T. M. Association between sleep hygiene and sleep quality in medical students. Behav Sleep Med 2010;8(2):113-121.
  23. Digdon, N. L. Circadian preference and college students' beliefs about sleep education. Chronobiol.Int 2010;27(2):297-317.
  24. Porkka-Heiskanen, T. Methylxanthines and sleep. Handb.Exp.Pharmacol 2011;(200):331-348.
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  26. Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 28;2:CD001792. doi: 10.1002/14651858.CD001792.pub3. Review.
  27. Sheppard SG. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994 Jul-Aug;11(4):379-85.
  28. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8..
  29. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
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Anxiety Psychiatric

Caffeine may lead to habituation and physical dependence, with amounts as low as 100 mg daily. An estimated 9% to 30% of caffeine consumers could be considered addicted to caffeine. Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, manic behavior, psychosis and panic attacks. Similar symptoms have been reported in a caffeine-naïve individual experiencing fatigue and dehydration after a dose of only 200 mg, with resolution of symptoms occurring within 2 hours.

Withdrawal: The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance. Headache is the most common symptom, due to cerebral vasodilation and increased blood flow. Other researchers suggest symptoms such as tiredness and fatigue, decreased energy, alertness and attentiveness, drowsiness, decreased contentedness, depressed mood, difficulty concentration, irritability, and lack of clear-headedness are typical of caffeine withdrawal. Withdrawal symptoms typically occur 12-24 hours after the last dose of caffeine and peak around 48 hours. Symptoms may persist for 2-9 days. Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon. In a case report, caffeine consumption of 560 mg daily was associated with increased suicidality.

  1. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
  2. Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch.Gen.Psychiatry 1991;48(7):611-617.
  3. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775.
  4. Garrett, B. E. and Griffiths, R. R. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology (Berl) 1998;139(3):195-202.
  5. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856.
  6. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35
  7. Natale, F., Cirillo, C., Di Marco, G. M., di Vetta, L. S., Aronne, L., Siciliano, A., Mocerino, R., Tedesco, M. A., Golino, P., and Calabro, R. When chewing gum is more than just a bad habit. Lancet 5-30-2009;373(9678):1918.
  8. Luebbe, A. M. and Bell, D. J. Mountain Dew or mountain don't?: a pilot investigation of caffeine use parameters and relations to depression and anxiety symptoms in 5th- and 10th-grade students. J Sch Health 2009;79(8):380-387.
  9. Skouroliakou, M., Bacopoulou, F., and Markantonis, S. L. Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial. J Paediatr.Child Health 2009;45(10):587-592.
  10. Boos, C. J., White, S. H., Bland, S. A., and McAllister, P. D. Dietary supplements and military operations: caution is advised. J R.Army Med Corps 2010;156(1):41-43.
  11. Suen, L. K., Tam, W. W., and Hon, K. L. Association of sleep hygiene-related factors and sleep quality among university students in Hong Kong. Hong.Kong.Med.J 2010;16(3):180-185.
  12. Stafford, L. D., Wright, C., and Yeomans, M. R. The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users. Psychol.Addict.Behav. 2010;24(2):274-281.
  13. Freire, R. C., Perna, G., and Nardi, A. E. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv.Rev.Psychiatry 2010;18(4):220-229.
  14. Li, S., Zhu, S., Jin, X., Yan, C., Wu, S., Jiang, F., and Shen, X. Risk factors associated with short sleep duration among Chinese school-aged children. Sleep Med. 2010;11(9):907-916.
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  16. Astorino, T. A., Martin, B. J., Schachtsiek, L., Wong, K., and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength.Cond.Res 2011;25(6):1752-1758.
  17. Youngstedt, S. D., O'Connor, P. J., Crabbe, J. B., and Dishman, R. K. Acute exercise reduces caffeine-induced anxiogenesis. Med.Sci Sports Exerc. 1998;30(5):740-745.
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  19. Hsu, C., Harden, R. N., and Houle, T. Nicotine and caffeine intake in complex regional pain syndrome. Journal of Back and Musculoskeletal Rehabilitation 2002;16(1):33-38.
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  22. Lystrup RM, Leggit JC. Caffeine toxicity due to supplement use in caffeine - naïve individual: a cautionary tale. Mil Med. 2015 Aug;180(8):e936-40.
  23. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61.
  24. Ozsungur, S., Brenner, D., and El-Sohemy, A. Fourteen well-described caffeine withdrawal symptoms factor into three clusters. Psychopharmacology (Berl) 2009;201(4):541-548.
  25. Aguggia, M. and Saracco, M. G. Pathophysiology of migraine chronification. Neurol.Sci 2010;31 Suppl 1:S15-S17.
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  27. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004;176:1-29.
  28. Lane, J. D. and Phillips-Bute, B. G. Caffeine deprivation affects vigilance performance and mood. Physiol Behav. 1998;65(1):171-175.
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Arrhythmia Cardiovascular

Caffeine can temporarily increase blood pressure. Usually, blood pressure increases 30 minutes after ingestion, peaks in 1-2 hours, and remains elevated for over 4 hours.

Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients. However, the form of caffeine may play a role in blood pressure increase after a more sustained caffeine use. In a pooled analysis of clinical trials, coffee intake was not associated with an increase in blood pressure, while ingesting caffeine 410 mg daily for at least 7 days modestly increased blood pressure by an average of 4.16/2.41 mmHg. Another meta-analysis of clinical research shows that taking caffeine increases systolic and diastolic blood pressure by approximately 2 mmHg when compared with control. Preliminary subgroup analyses suggest that caffeine may increase blood pressure more in males or at doses over 400 mg.

When used prior to intensive exercise, caffeine can increase systolic blood pressure by 7-8 mmHg. The blood pressure-raising effects of caffeine are greater during stress and after caffeine-abstinence of at least 24 hours.

Epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension. Habitual coffee consumption also doesn't seem to be related to hypertension, but habitual consumption of sugared or diet cola is associated with development of hypertension.

Epidemiological research has found that regular caffeine intake of up to 400 mg daily is not associated with increased incidence of atrial fibrillation, atherosclerosis, cardiac ectopy, stroke, ventricular arrhythmia, and cardiovascular disease in general. One clinical trial shows that in adults with diagnosed heart failure, consumption of 500 mg of coffee does not result in an increased risk for arrhythmia during exercise. However, caffeine intake may pose a greater cardiovascular risk to subjects that are not regular users of caffeine. For example, in one population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects that don't regularly drink coffee. In a population study in Japanese subjects, caffeine-containing medication use was modestly associated with hemorrhagic stroke in adults that do not consume caffeine regularly.

The most common side effect of caffeine in neonates receiving caffeine for apnea is tachycardia.

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  5. Quinlan, P., Lane, J., and Aspinall, L. Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type. Psychopharmacology (Berl) 1997;134(2):164-173.
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  7. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63.
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  14. Li-Neng, Y., Greenstadt, L., and Shapiro, D. Effects of caffeine on blood pressure:A cross-cultural comparison. Psychophysiology 1983;20
  15. Whitsett, T. L., Manion, C. V., and Christensen, H. D. Cardiovascular effects of coffee and caffeine. Am.J.Cardiol. 3-15-1984;53(7):918-922.
  16. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622.
  17. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5.
  18. Conen, D., Chiuve, S. E., Everett, B. M., Zhang, S. M., Buring, J. E., and Albert, C. M. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92(3):509-514.
  19. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038.
  20. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383-9. doi: 10.1136/heartjnl-2013-303950. Re
  21. Cheng M, Hu Z, Lu X, Huang J, Gu D. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol. 2014 Apr;30(4):448-54. doi: 10.1016/j.cjca.2013.12.026. Epub 2014 2. Review.
  22. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of
  23. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32.
  24. Krittanawong C, Tunhasiriwet A, Wang Z, et al. Is caffeine or coffee consumption a risk for new-onset atrial fibrillation? A systematic review and meta-analysis. Eur J Prev Cardiol. 2020:2047487320908385.
  25. Reis, J. P., Loria, C. M., Steffen, L. M., Zhou, X., van, Horn L., Siscovick, D. S., Jacobs, D. R., Jr., and Carr, J. J. Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. A
  26. Dixit S, Stein PK, Dewland TA, Dukes JW, Vittinghoff E, Heckbert SR, Marcus GM. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc. 2016 26;5(1). pii: e002503. doi: 10.1161/JAHA.115.002503.
  27. Lopez-Garcia, E., Rodriguez-Artalejo, F., Rexrode, K. M., Logroscino, G., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of stroke in women. Circulation 3-3-2009;119(8):1116-1123.
  28. Zuchinali P, Riberio PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE. Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace 2016 Feb;18(2):257-66.
  29. Zhang, W., Lopez-Garcia, E., Li, T. Y., Hu, F. B., and van Dam, R. M. Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes. Diabetes Care 2009;32(6):1043-1045.
  30. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648.
  31. Zuchinali P, Souza GC, Pimentel M, et al. Short-term effects of high-dose caffeine on cardiac arrhythmias in patients with heart failure: a randomized clinical trial. JAMA Intern Med. 2016 Dec 1;176(12):1752-59.
  32. Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., and Mittleman, M. A. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 11-2-2010;75(18):1583-1588.
  33. Lee SM, Choi NK, Lee BC, Cho KH, Yoon BW, Park BJ. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke. 2013 Aug;44(8):2139-43. doi: 10.1161/STROKEAHA.111.674077. Epub 2013 6.
  34. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018;103(6):F523-9. doi: 10.1136/archdischild-2017-313556.
  35. Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol 2024;44(6):785-801.
Bladder cancer Oncologic

Most human studies which have examined caffeine or methylxanthine intake have found that they do not play a role in the development of various cancers, including breast, ovarian, brain, colon, rectal, or bladder cancer.

  1. Tavani, A. and La, Vecchia C. Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003. Cancer Causes Control 2004;15(8):743-757.
  2. Ganmaa, D., Willett, W. C., Li, T. Y., Feskanich, D., van Dam, R. M., Lopez-Garcia, E., Hunter, D. J., and Holmes, M. D. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 5-1-2008;122(9):2071-2076.
  3. Ishitani, K., Lin, J., Manson, J. E., Buring, J. E., and Zhang, S. M. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 10-13-2008;168(18):2022-2031.
  4. Holick, C. N., Smith, S. G., Giovannucci, E., and Michaud, D. S. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies. Cancer Epidemiol.Biomarkers Prev 2010;19(1):39-47.
  5. Boggs, D. A., Palmer, J. R., Stampfer, M. J., Spiegelman, D., Adams-Campbell, L. L., and Rosenberg, L. Tea and coffee intake in relation to risk of breast cancer in the Black Women's Health Study. Cancer Causes Control 2010;21(11):1941-1948.
  6. Lubin, F. and Ron, E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53(2-3):81-90.
  7. Fraumeni, J. F., Jr., Scotto, J., and Dunham, L. J. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204.
  8. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013 Jun;129(3):620-9. doi: 10.1016/j.ygyno.2013.03.014. Epub 2013 25. Review.
  9. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli
  10. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044.
Bone loss Musculoskeletal

Caffeine can induce or exacerbate muscular tremors. There has also been a report of severe rhabdomyolysis in a healthy 40-year-old patient who consumed an energy drink containing 400 mg of caffeine (4 mg/kg) and then participated in strenuous weightlifting exercise.

Epidemiological evidence regarding the relationship between caffeine use and the risk for osteoporosis is contradictory. Caffeine can release calcium from storage sites and increase its urinary excretion. Females with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass. However, moderate caffeine intake, less than 300 mg daily, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake. Premature infants treated with intravenous caffeine for apnea of prematurity, have a lower bone mineral content compared with infants who are not treated with caffeine, especially when treatment extends beyond 14 days.

  1. Duvnjak-Zaknich, D. M., Dawson, B. T., Wallman, K. E., and Henry, G. Effect of caffeine on reactive agility time when fresh and fatigued. Med.Sci.Sports Exerc. 2011;43(8):1523-1530.
  2. Morgan, J. C. and Sethi, K. D. Drug-induced tremors. Lancet Neurol. 2005;4(12):866-876.
  3. Kivity, S., Ben Aharon, Y., Man, A., and Topilsky, M. The effect of caffeine on exercise-induced bronchoconstriction. Chest 1990;97(5):1083-1085.
  4. Tinawi M. Severe Rhabdomyolysis Due to Strenuous Exercise With a Potential Role of a High-Caffeine Energy Drink. Cureus 2022;14(1):e20867.
  5. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700.
  6. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70.
  7. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4.
  8. Ismail RIH, Awad HA, Saber M, Shehata BM. Bone mineral content for preterm neonates treated with caffeine using dual energy X-ray absorptiometry: An observational study. J Neonatal Perinatal Med 2023;16(1):129-135.
  9. Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr 2000;19:256-61.
Breast cancer Endocrine

Some evidence shows caffeine is associated with fibrocystic breast disease or breast cancer in females; however, this is controversial since findings are conflicting. Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain. A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors. Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer.

Clinical research in healthy adults shows that an increase consumption of caffeine results in increased insulin resistance.

  1. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4.
  2. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044.
  3. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80.
  4. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389.
  5. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9.
Diarrhea Gastrointestinal

Gastrointestinal upset, nausea, diarrhea, abdominal pain, and fecal incontinence may occur with caffeine intake. Also, caffeine may cause feeding intolerance and gastrointestinal irritation in infants. Perioperative caffeine during cardiopulmonary bypass surgery seems to increase the rate of postoperative nausea and vomiting. Caffeine and coffee consumption have been associated with an increase in the incidence of heartburn and gastrointestinal esophageal reflux disease (GERD).

  1. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97.
  2. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3
  3. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216.
  4. Tunnicliffe, J. M., Erdman, K. A., Reimer, R. A., Lun, V., and Shearer, J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab 2008;33(6):1301-1310.
  5. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535.
  6. Astorino, T. A., Martin, B. J., Schachtsiek, L., Wong, K., and Ng, K. Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength.Cond.Res 2011;25(6):1752-1758.
  7. Duvnjak-Zaknich, D. M., Dawson, B. T., Wallman, K. E., and Henry, G. Effect of caffeine on reactive agility time when fresh and fatigued. Med.Sci.Sports Exerc. 2011;43(8):1523-1530.
  8. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092.
  9. Magdalan J, Zawadzki M, Skowronek R, et al. Nonfatal and fata intoxications with pure caffeine - report of three different cases. Forensic Sci Med Pathol. 2017 Sep;13(3):355-58.
  10. Trexler ET, Smith-Ryan AE, Roelofs EJ, Hirsch KR, Persky AM, Mock AG. Effects of coffee and caffeine anhydrous intake during creatine loading. J Strength Cond Res. 2016 May;30(5):1438-46.
  11. Tobias JD. Caffeine in the treatment of apnea associated with respiratory syncytial virus infection in neonates and infants. South Med J 2000;93:297-304.
  12. Lagier D, Nee L, Guieu R, et al. Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: a randomized controlled clinical trial. Eur J Anaesthesiol. 2018 Apr 26. [Epub ahead of
  13. Boekema, P. J., Samsom, M., van Berge Henegouwen, G. P., and Smout, A. J. Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol.Suppl 1999;230:35-39.
  14. Terry, P., Lagergren, J., Wolk, A., and Nyren, O. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Nutr Cancer 2000;38(2):186-191.
  15. Thomas, F. B., Steinbaugh, J. T., Fromkes, J. J., Mekhjian, H. S., and Caldwell, J. H. Inhibitory effect of coffee on lower esophageal sphincter pressure. Gastroenterology 1980;79(6):1262-1266.
  16. Cohen, S. Pathogenesis of coffee-induced gastrointestinal symptoms. N.Engl.J Med 7-17-1980;303(3):122-124.
  17. Feldman, M. and Barnett, C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterology 1995;108(1):125-131.
  18. Richter, J. E., Katz, P. O., and Waring, J. P. Gastroesophageal Reflux Disease. IFFGD 2000;
  19. Naliboff, B. D., Mayer, M., Fass, R., Fitzgerald, L. Z., Chang, L., Bolus, R., and Mayer, E. A. The effect of life stress on symptoms of heartburn. Psychosom.Med 2004;66(3):426-434.
  20. Wang, J. H., Luo, J. Y., Dong, L., Gong, J., and Tong, M. Epidemiology of gastroesophageal reflux disease: a general population-based study in Xi'an of Northwest China. World J Gastroenterol. 6-1-2004;10(11):1647-1651.
  21. DiBaise, J. K. A randomized, double-blind comparison of two different coffee-roasting processes on development of heartburn and dyspepsia in coffee-sensitive individuals. Dig.Dis.Sci 2003;48(4):652-656.
Glaucoma Ocular/Otic

In individuals with glaucoma, coffee consumption and caffeine intake has been found to increase intraocular pressure. The magnitude of this effect seems to depend on individual tolerance to caffeine. Some research in healthy young adults shows that caffeine increases intraocular pressure to a greater degree in low-consumers of caffeine (i.e., 1 cup of coffee or less daily) when compared to high-consumers (i.e., those consuming 2 cups of coffee or more daily). The peak increase of intraocular pressure seems to occur at about 1.5 hours after caffeine ingestion, and there is no notable effect 4 hours after ingestion.

  1. Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5..
  2. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681.
  3. Higginbotham, E. J., Kilimanjaro, H. A., Wilensky, J. T., Batenhorst, R. L., and Hermann, D. The effect of caffeine on intraocular pressure in glaucoma patients. Ophthalmology 1989;96(5):624-626.
  4. Chandrasekaran, S., Rochtchina, E., and Mitchell, P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. J Glaucoma. 2005;14(6):504-507.
  5. Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis. J Sci Med Sport. 2019;22(2):232-238.
  6. Adams, B. A. and Brubaker, R. F. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology 1990;97(8):1030-1031.
Interstitial cystitis Genitourinary

Caffeine, a known diuretic, may increase voiding, give a sense of urgency, and irritate the bladder. In men with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome. Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily was associated with increased severity of premenstrual syndrome. Finally, population research shows that exposure to caffeine was not associated with an increased risk of endometriosis.

  1. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433.
  2. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  3. Stojanovic E, Scanlan AT, Milanovic Z, Fox JL, Stankovic R, Dalbo VJ. Acute caffeine supplementation improves jumping, sprinting, and change-of-direction performance in basketball players when ingested in the morning but not evening. Eur J Sport Sci. 2021
  4. Li, G. Z., Zhang, N., Du, P., Yang, Y., Wu, S. L., Xiao, Y. X., Jin, R., Liu, L., Shen, H., and Dai, Y. Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. Chin Med
  5. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110.
  6. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, Viganò P, La Vecchia C. Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr. 2014 Oct;53(7):1573-9. doi: 10.1007/s00394-014-0662-7. Epub 2014 31.
Kidney stones (nephrolithiasis) Renal

Data on the relationship between caffeine intake and kidney stones are conflicting. Some clinical research shows that caffeine consumption may increase the risk of stone formation, while other research shows a reduced risk with increasing caffeine intakes. A meta-analysis of 7 studies found that overall, there is an inverse relationship, with a 32% decrease in the risk of kidney stones between the lowest and highest daily intakes of caffeine.

  1. Massey, L. K. and Sutton, R. A. Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers. J.Urol. 2004;172(2):555-558.
  2. Zhao J, Huang Y, Yu X. Caffeine intake and the risk of incident kidney stones: a systematic review and meta-analysis. Int Urol Nephrol 2022;54(10):2457-2466.
Urticaria Dermatologic

There are several case reports of urticaria after caffeine ingestion.

  1. Caballero, T., Garcia-Ara, C., Pascual, C., Diaz-Pena, J. M., and Ojeda, A. Urticaria induced by caffeine. J.Investig.Allergol.Clin Immunol. 1993;3(3):160-162.
  2. Quirce, G. S., Freire, P., Fernandez, R. M., Davila, I., and Losada, E. Urticaria from caffeine. J.Allergy Clin Immunol. 1991;88(4):680-681.
  3. Pola, J., Subiza, J., Armentia, A., Zapata, C., Hinojosa, M., Losada, E., and Valdivieso, R. Urticaria caused by caffeine. Ann.Allergy 1988;60(3):207-208.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Adverse-effects data: Natural Medicines, Therapeutic Research Center

Dosing

There is no single "correct" dose of caffeine, and the right amount depends on your age, health, and how sensitive you are. Many health authorities suggest that moderate daily intake is reasonable for most healthy adults, but individual limits vary widely.

If you use a caffeine supplement, energy drink, or pre-workout powder, follow the directions on the product label and do not take more than recommended. Concentrated caffeine powders are especially dangerous because a small mistake can lead to a harmful overdose.

Remember that caffeine adds up across coffee, tea, sodas, energy drinks, chocolate, and any supplements or medicines that contain it. If you are unsure how much is safe for you, talk to your pharmacist or doctor.

Pregnancy & Breastfeeding

Caffeine & Pregnancy

Possibly Safe

When used orally in amounts commonly found in foods. Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen. Fetal blood and tissue levels are similar to maternal concentrations. The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects. In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage. This increased risk seems to occur in those with genotypes that confer a slow rate of caffeine metabolism. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations. However, observational research in a Norwegian cohort found that caffeine consumption is associated with a 16% increased odds of the baby being born small for gestational age when compared with no consumption. The same Norwegian cohort found that low to moderate caffeine consumption during pregnancy is not associated with changes in neurodevelopment in children up to 8 years of age. Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea.

  1. Kujawa-Hadrys, M., Tosik, D., and Bartel, H. Changes in thickness of each layer of developing chicken cornea after administration of caffeine. Folia Histochem.Cytobiol. 2010;48(2):273-277.
  2. Linn, S., Schoenbaum, S. C., Monson, R. R., Rosner, B., Stubblefield, P. G., and Ryan, K. J. No association between coffee consumption and adverse outcomes of pregnancy. N.Engl.J Med 1-21-1982;306(3):141-145.
  3. Chen L, Bell EM, Browne ML, Druschel CM, Romitti PA, Schmidt RJ, Burns TL, Moslehi R, Olney RS; National Birth Defects Prevention Study. Maternal caffeine consumption and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol. 2012 De
  4. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  5. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  6. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44.
  7. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9.
  8. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44.
  9. Bracken MB, Triche EW, Belanger K, et al. Association of maternal caffeine consumption with decrements in fetal growth. Am J Epidemiol 2003;157:456-66..
  10. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8.
  11. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62.
  12. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648.
  13. Hinkle SN, Gleason JL, Yisahak SF, et al. Assessment of Caffeine Consumption and Maternal Cardiometabolic Pregnancy Complications. JAMA Netw Open 2021;4(11):e2133401.
  14. Greenwood, D. C., Alwan, N., Boylan, S., Cade, J. E., Charvill, J., Chipps, K. C., Cooke, M. S., Dolby, V. A., Hay, A. W., Kassam, S., Kirk, S. F., Konje, J. C., Potdar, N., Shires, S., Simpson, N., Taub, N., Thomas, J. D., Walker, J., White, K. L., and
  15. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30.
  16. Modzelewska D, Bellocco R, Elfvin A, et al. Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome - results from the Norwegian Mother and Child Cohort Study. BMC Pregnancy Childbirth. 2019;19(1):80.
  17. Jin F, Qiao C. Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. Int J Obes (Lond). 2020.
  18. Berglundh S, Vollrath M, Brantsæter AL, et al. Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study. Eur J Nutr. 2020.
Possibly Unsafe

When used orally in amounts over 300 mg daily. Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels. Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies. Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Additionally, high doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants. High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight. In a cohort of mother/infant pairs with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In another cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights.

  1. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  2. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 2017;109:585-648.
  3. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1-8.
  4. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4..
  5. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44.
  6. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44.
  7. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 2014 19;12:174. doi: 10.1186/s12916-014-0174-6
  8. Greenwood DC, Thatcher NJ, Ye J, Garrard L, Keogh G, King LG, Cade JE. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2014;29(10):725-34. doi: 10.1007/s10654-014-9944-x.
  9. Rhee J, Kim R, Kim Y, et al. Maternal caffeine consumption during pregnancy and risk of low birth weight: a dose-response meta-analysis of observational studies. PLoS One. 2015 Jul 20;10(7):e0132334.
  10. Gleason JL, Sundaram R, Mitro SD, et al. Association of maternal caffeine consumption during pregnancy with child growth. JAMA Netw Open. 2022;5(10):e2239609.

Caffeine & Breastfeeding

Possibly Safe

When used orally in amounts commonly found in foods. Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations and caffeine peaks in breastmilk approximately 1-2 hours after consumption.

  1. Bailey, D. N., Weibert, R. T., Naylor, A. J., and Shaw, R. F. A study of salicylate and caffeine excretion in the breast milk of two nursing mothers. J.Anal.Toxicol. 1982;6(2):64-68.
Possibly Unsafe

When used orally in large amounts. Caffeine is excreted slowly in infants and may accumulate. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants exposed to caffeine.

  1. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  2. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

© 2026 Therapeutic Research Center

Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center

References & further reading

The 236 references that drive our Caffeine monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed
Keep reading

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.

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

Brand directory

Brands that make products with Caffeine

1,214 brands in our database make a supplement containing Caffeine.

Product directory

Supplement products with Caffeine

6,878 products in our database contain Caffeine. Open any to see its full ingredient list and every drug interaction we check.

Active Metabolism by Bayer One A Day Women's Tablet Or Pill 50 Tablet(s) View ingredients & interactions Active Mind by Nature's Bounty Other (e.g. Tea Bag) 60 Coated Caplet(s) View ingredients & interactions Active Peach Mango by Plexus Powder 15 Single Serve Packet(s) View ingredients & interactions Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals Softgel Capsule 60 Liquid Soft-Gel(s) View ingredients & interactions ActiveMind by Puritan's Pride Other (e.g. Tea Bag) 60 Coated Caplet(s) View ingredients & interactions Activize Oxyplus Natural Black Currant Flavoured by FitLine Powder 6.17 Ounce(s) · 175 Gram(s) View ingredients & interactions Adam's Virility by Logos Nutritionals Capsule 60 Capsule(s) View ingredients & interactions Adderex XR by HTP Hi-Tech Pharmaceuticals Tablet Or Pill 30 Tablet(s) View ingredients & interactions AdderRx by NexGen Capsule 30 Capsule(s) View ingredients & interactions Adderzol XR by Aggressive Labz Capsule 90 Capsule(s) View ingredients & interactions Adipodex by Nutrex Research Capsule 45 Capsule(s) View ingredients & interactions Adipropen Ultra by 8WeeksOut Capsule 90 Capsule(s) View ingredients & interactions AdreN.O. Blue Razz by BlackMarket Powder View ingredients & interactions AdreN.O. Fruit Punch by BlackMarket Powder View ingredients & interactions AdreN.O. Watermelon by BlackMarket Powder View ingredients & interactions AdreN.O.lyn Underground Grape Lime Rickey by BlackMarket Powder 13.89 Ounce(s) · 394 Gram(s) View ingredients & interactions Adrenal Rush V2 Pineapple Mango by Primeval Labs Powder 246 Gram(s) View ingredients & interactions Adrenaline Chase by Relentless Pursuit RP Capsule 30 Capsule(s) View ingredients & interactions Adrenaline XR by Fight Labs Capsule 60 Capsule(s) View ingredients & interactions Adult by BrainStrong Softgel Capsule 120 DHA Softgel(s) View ingredients & interactions Adult by BrainStrong Softgel Capsule 90 DHA Softgel(s) View ingredients & interactions Advanced ACV Plus by Botanic Choice Capsule 90 Capsule(s) View ingredients & interactions Advanced ACV Plus by Indiana Botanic Gardens Capsule 45 Capsule(s) View ingredients & interactions Advanced Caffeine by Prolab Tablet Or Pill 120 Tablet(s) View ingredients & interactions
Pharmacist Counseling Corner

Caffeine: Common Questions

What is Caffeine used for, and does it work?
People use Caffeine for many reasons, but the evidence varies by use. According to the Natural Medicines database, there is at least some clinical evidence supporting Caffeine for Neonatal apnea, Postoperative headache, Athletic performance and Mental alertness. For most other uses it has been studied for, the evidence is currently insufficient to rate. See the graded list on this page, and always confirm with your pharmacist or doctor.
Does Caffeine interact with prescription medications?
Yes. We list 655 medications with a known interaction with Caffeine, including 8 rated major. Use the checker above to see how Caffeine interacts with a specific drug.
How are Caffeine interactions rated?
Each interaction is graded major, moderate, or minor based on how clinically significant it is and the strength of the evidence behind it. Major interactions are the most serious and are best avoided, or used only under close professional supervision.
Is it safe to take Caffeine with my medications?
It depends on the specific medication. Some combinations are fine, while others call for monitoring, timing changes, or should be avoided. Check your exact drug above and confirm with your pharmacist or doctor before starting, stopping, or changing anything.
Where does this Caffeine interaction information come from?
Our interaction data is built on the Natural Medicines database — an evidence-graded reference for vitamins, herbs, and supplements — and is reviewed by licensed HelloPharmacist pharmacists, who may add clinical context.
How much Caffeine is safe to have in a day?
For most healthy adults, moderate daily intake is usually considered acceptable, but the right amount varies from person to person. People who are pregnant, sensitive to Caffeine, or have heart or anxiety problems should have less and check with their doctor.
Can I have Caffeine while pregnant?
Many experts advise limiting Caffeine during pregnancy, since high amounts have been linked to certain risks. Talk to your doctor about a safe limit for you, and remember that coffee, tea, sodas, and chocolate all add up.
Why do I get a headache when I skip my coffee?
If you use Caffeine regularly and then stop, you can get withdrawal symptoms like headache, tiredness, and irritability for a few days. Cutting back slowly instead of stopping all at once can help.
Is Caffeine addictive?
Caffeine can cause physical dependence, meaning your body gets used to it and you may have withdrawal symptoms if you stop suddenly. This is generally milder than addiction to many other substances, but you can still feel a strong urge for your usual amount.

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

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A rotating sample of real supplements in our database that list Caffeine — open any to see its full ingredients and every drug interaction we check.

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