Major interaction on record — check this product against your medications before combining. Check your meds →
Dietary supplement

Ortho Heart Ingredients & Drug Interactions

by AOR Advanced Orthomolecular Research Advanced

Capsule Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Ortho Heart is a dietary supplement by AOR Advanced Orthomolecular Research Advanced with 7 active ingredients. Its ingredients are commonly taken for common cold and immune support, antioxidant support, skin health and collagen formation.Based on those ingredients, 1,428 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Hibiscus (Hibiscus sabdariffa) extract, Garlic Bulb Extract, Green Coffee bean extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Ortho Heart by AOR Advanced Orthomolecular Research Advanced

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 8 of its 8 active ingredients.
  • “Garlic Bulb Extract” is listed as a grouped ingredient — the label gives one combined amount (100 mg) without saying how much of each component you get.
  • “Green Coffee bean extract” is listed as a grouped ingredient — the label gives one combined amount (400 mg) without saying how much of each component you get.

Ortho Heart contains 8 active ingredients. Vitamin C supports immune function and acts as an antioxidant.

Caffeine is a stimulant that increases alertness. The product also includes garlic bulb extract and green coffee bean extract (which contain allicin and chlorogenic acid respectively), along with potassium, nitrate, L-theanine (an amino acid), and hibiscus extract.

The inactive ingredients are microcrystalline cellulose, a capsule, silicon dioxide, sodium stearyl fumarate, and maltodextrin.

Does it work?

Moderate evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: cardiovascular health and heart support.
  • We looked for evidence on: Atherosclerosis, Cardiovascular disease (CVD), Coronary heart disease (CHD), Coronary artery bypass graft (CABG) surgery, hypertension, hyperlipidemia — and 1 related terms.
  • The strongest evidence on file: Hibiscus Sabdariffa is rated "Possibly Effective" for Hypertension (Natural Medicines).
  • Also on file: Vitamin C is rated "Possibly Effective" for Hypertension.
  • Also on file: Vitamin C is rated "Possibly Ineffective" for Atherosclerosis, Cardiovascular disease (CVD).

Vitamin C is effective for vitamin C deficiency and possibly effective for anemia, atrial fibrillation, cataracts, and exercise-related respiratory infections. Caffeine is effective for neonatal apnea and postoperative headache, and likely effective for mental alertness and athletic performance.

L-theanine is possibly effective for cognitive function but has insufficient evidence for age-related cognitive decline, Alzheimer disease, anxiety, OCD, and cancer. Hibiscus extract is possibly effective for high blood pressure but has insufficient evidence for weight loss, kidney stones, and metabolic syndrome.

We hold no effectiveness data for potassium, garlic, green coffee extract, allicin, chlorogenic acid, or nitrate in this product.

The evidence, ingredient by ingredient Vitamin C Garlic Coffee Caffeine Potassium Theanine Hibiscus Sabdariffa

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 5 of the 5 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 5 of 5.
  • General safety write-ups exist for 5 of 5.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Vitamin C is generally well tolerated at normal doses but very high doses can cause abdominal cramps, heartburn, diarrhea, and kidney stones, especially in people prone to them. Caffeine is generally safe in moderate amounts for healthy adults but can cause anxiety, jitteriness, insomnia, and restlessness; high doses carry rare risks of stroke.

Potassium from food is safe, but supplements can cause dangerously high blood levels (hyperkalemia), especially in people with kidney disease, leading to heart rhythm problems and confusion. L-theanine may cause headaches or drowsiness.

Hibiscus extract is generally well tolerated as a tea but concentrated extracts warrant caution. During pregnancy, avoid high-dose vitamin C supplements and medicinal amounts of hibiscus; potassium from food is fine but supplements should be used only under medical guidance, and there isn't enough safety data for L-theanine.

During breastfeeding, caffeine passes into milk in small amounts (usually acceptable with moderate intake), and there isn't enough data on L-theanine or hibiscus.

Side effects, ingredient by ingredient Vitamin C Garlic Coffee Caffeine Potassium Theanine Hibiscus Sabdariffa

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 5 of the 5 matched ingredients can interact with medications — Hibiscus Sabdariffa, Potassium, Caffeine, Vitamin C, Theanine.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; cancer treatments; diabetes medications; lithium.
  • For scale: 1,421 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, check with your doctor or pharmacist if you take ephedrine or other stimulants (Major-severity risk with caffeine), chloroquine (Major-severity risk with hibiscus), or blood pressure medications including ACE inhibitors, ARBs, or potassium-sparing diuretics (Moderate risk from potassium). Also double-check if you use birth control or hormone therapy, blood thinners, thyroid medication, diabetes drugs, cholesterol medication, antiseizure drugs, sleep aids, or certain antibiotics.

No interactions are documented for the allicin, chlorogenic acid, or nitrate in this product.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Ortho Heart may help with heart-related goals through its potassium, hibiscus, and other ingredients, but you need to check it against your medications first—especially if you take blood pressure drugs, diabetes medications, blood thinners, birth control, hormone therapy, antiseizure drugs, or antimalarial drugs. Talk with your doctor or pharmacist before starting it to make sure it's safe for you personally.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 5 of 8 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 24, 2020.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Ortho Heart, straight from the product label.

Brand AOR Advanced Orthomolecular Research Advanced
Barcode (UPC) 624917082883
Net contents 60 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Mar 24, 2020
DSLD ID 214844
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Women (not pregnant or lactating), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Ortho Heart by AOR Advanced Orthomolecular Research Advanced, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
Servings per container
60
UPC/BARCODE
624917082883
IngredientAmount% DV
Vitamin C100 mg, 50 mg111%, 56%
Caffeine4 mg, 2 mg--
Garlic Bulb Extract100 mg, 50 mg--
Green Coffee bean extract400 mg, 200 mg--
Allicin1 mg, 0.5 mg--
Chlorogenic Acid200 mg, 100 mg--
Potassium167 mg, 83.5 mg4%, 2%
Nitrate259 mg, 129.5 mg--
L-Theanine200 mg, 100 mg--
Hibiscus (Hibiscus sabdariffa) extract9.6 mg, 4.8 mg--

Other ingredients: Microcrystalline Cellulose, Capsule, Silicon Dioxide, Sodium Stearyl Fumarate, Maltodextrin

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Formulation

GMP Manufacturing Quality assured Independent testing

Supports cardiovascular health

Vegan

Gluten free

AOR guarantees that all ingredients have been declared on the label.

Made without wheat, gluten, peanuts, sulfites, soy, dairy, eggs, fish, shellfish or any animal byproduct.

Precautions

Do not use if safety seal is broken

Warning: Do not take if pregnant or lactating. Consult a health care practitioner prior to use if you have a medical condition (eg. Diabetes) or if you’re taking medications (eg. blood thinners, protease inhibitors.)

Do not take with erectile dysfunction-type products.

Keep out of reach of children.

Caution: Hypersensitivity (e.g. allergy) has been known to occur; in which case discontinue use.

To report a serious adverse event or obtain product information, call 1-866-215-0450

Storage

Store tightly sealed in a cool, dry place

Formula

Discussion: Ortho Heart is a well-rounded formula combining scientifically studied ingredients with those used in herbal medicine and based on diets known to promote cardiovascular health, such as the Mediterranean diet.

Suggested/Recommended/Usage/Directions

Directions: Take 1 capsule 1-2 times daily with food, or as directed by a qualified health care professional.

FDA Disclaimer Statement

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

FDA Statement of Identity

Dietary Supplement

General Statements

Product of Canada

See for yourself

Ortho Heart by AOR Advanced Orthomolecular Research Advanced label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

What’s inside

The Ingredients in Ortho Heart by AOR Advanced Orthomolecular Research Advanced

These are the 7 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Servings per container60 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Vitamin C

Interacts with
207 drugs
100 mg per serving Form: Ascorbic Acid

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Garlic Bulb Extract

Interacts with
989 drugs
100 mg per serving

Garlic is a common food and supplement that may modestly help with blood pressure and cholesterol, though the evidence is mixed and effects are usuall...

Garlic Bulb Extract monograph & interactions
  • › Allicin

Green Coffee bean extract

Interacts with
591 drugs
400 mg per serving

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healt...

Green Coffee bean extract monograph & interactions

Potassium

Interacts with
62 drugs
167 mg per serving Form: Potassium Nitrate

Potassium is an essential mineral your body needs for nerve signals, muscle function, and a steady heartbeat, and most people get enough from a balanc...

Potassium monograph & interactions

Nitrate

259 mg per serving Form: Potassium Nitrate

L-Theanine

Interacts with
565 drugs
200 mg per serving Form: Green Tea

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong dro...

L-Theanine monograph & interactions

Hibiscus (Hibiscus sabdariffa) extract

Interacts with
1,087 drugs
9.6 mg per serving

Hibiscus sabdariffa is a tart, cranberry-flavored plant most often consumed as a tea, and its best-studied use is for mildly lowering blood pressure....

Hibiscus (Hibiscus sabdariffa) extract monograph & interactions

Other (inactive) ingredients: Microcrystalline Cellulose, Capsule, Silicon Dioxide, Sodium Stearyl Fumarate, Maltodextrin. These complete the product’s ingredient list but are not active constituents.

Interaction report

Ortho Heart by AOR Advanced Orthomolecular Research Advanced Drug Interactions

Want to check YOUR meds against Ortho Heart?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

Go to the checker
1,428Drugs
10 Major 1,197 Moderate 221 Minor

Ingredients driving the most interactions

Vitamin C 207

Each ingredient & the kinds of drugs it affects

For each ingredient in Ortho Heart with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Hibiscus (Hibiscus sabdariffa) extract16 drug types · 1,087 drugs

Chloroquine (Aralen)

Taking Hibiscus sabdariffa tea along with chloroquine seems to reduce levels of chloroquine.
When taken together, Hibiscus sabdariffa tea significantly reduces the bioavailability of chloroquine. This may reduce its clinical effects. People taking chloroquine for the treatment or prevention of malaria should avoid Hibiscus sabdariffa tea.

Likelihood Probable Evidence B
Antidiabetes Drugs

Theoretically, taking Hibiscus sabdariffa with antidiabetes drugs might increase the risk of hypoglycemia.
Most clinical research shows that Hibiscus sabdariffa can reduce blood glucose levels.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking Hibiscus sabdariffa with antihypertensive drugs might increase the risk of hypotension.
Most clinical evidence suggests that taking Hibiscus sabdariffa reduces systolic and diastolic blood pressure. In animal research, Hibiscus sabdariffa increased the hypotensive effects of single doses of losartan and amlodipine.

Likelihood Possible Evidence D
Diclofenac (Voltaren, Others)

Taking Hibiscus sabdariffa with diclofenac may increase the levels and adverse effects of diclofenac.
Pharmacokinetic research in humans shows that drinking a beverage made with Hibiscus sabdariffa flowers reduces the excretion of diclofenac by approximately 38% when compared with water. The clinical significance of this is unknown.

Likelihood Possible Evidence B
Losartan (Cozaar)

Theoretically, Hibiscus sabdariffa might increase the levels and clinical effects of losartan.
Animal research in rats with laboratory-induced hypertension shows that providing Hibiscus sabdariffa for 14-17 days prior to a single administration with losartan modestly increases losartan concentrations and increases hypotensive effects when compared with a single administration of losartan alone. It is not clear if Hibiscus sabdariffa alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Likelihood Possible Evidence D
Simvastatin (Zocor)

Taking Hibiscus sabdariffa with simvastatin might reduce the levels and clinical effects of simvastatin.
A pharmacokinetic study in humans shows that taking a beverage prepared with dried Hibiscus sabdariffa flower 300 grams concurrently with a single dose of simvastatin 40 mg increases the clearance of simvastatin by about 45% and reduces peak levels of simvastatin by 18%.

Likelihood Probable Evidence B
Acetaminophen (Tylenol, Others)

Theoretically, taking Hibiscus sabdariffa with acetaminophen might decrease the clinical effects of acetaminophen.
There is some evidence that consuming a Hibiscus sabdariffa beverage (Zobo drink) before taking acetaminophen can decrease the elimination half-life of acetaminophen. Hibiscus sabdariffa does not seem to decrease maximum concentration or area under the curve of acetaminophen. The clinical significance of this is unknown.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP1A2 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP1A2. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2A6 (Cyp2A6) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2A6 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2A6. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2B6 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2B6. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2C19 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2C19. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C8 (Cyp2C8) Substrates

Theoretically, Hibiscus sabdariffa might reduce the metabolism of CYP2C8 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2C8. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2C9 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2C9. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2D6 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2D6. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP2E1 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP2E1. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, Hibiscus sabdariffa extract might reduce the metabolism of CYP3A4 substrates.
In vitro research shows that Hibiscus sabdariffa calyx extract inhibits CYP3A4. This interaction has not been reported in humans.

Likelihood Possible Evidence D

Garlic Bulb Extract12 drug types · 989 drugs

Anticoagulant/Antiplatelet Drugs

Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that garlic and garlic extract lower blood glucose levels in healthy and diabetic individuals.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
In human research, both garlic and garlic extracts have blood pressure-lowering effects.

Likelihood Possible Evidence D
Atazanavir (Reyataz)

Theoretically, garlic might decrease levels and effects of atazanavir.
In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Garlic might increase levels of drugs metabolized by CYP2E1.
Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39%. Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa. Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels. Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Likelihood Possible Evidence B
Isoniazid

Theoretically, garlic might decrease levels of isoniazid.
Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa; however, the exact mechanism of this potential interaction is not known.

Likelihood Possible Evidence D
Protease Inhibitors (Pis)

Theoretically, garlic products containing allicin might decrease levels of PIs.
Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa. Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Likelihood Possible Evidence B
Saquinavir (Fortovase, Invirase)

Theoretically, garlic containing allicin might decrease levels of saquinavir.
Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa. Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin. Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.

Likelihood Possible Evidence B
Sofosbuvir (Sovaldi)

Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, garlic might increase levels of tacrolimus.
In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Theoretically, garlic might increase the risk of bleeding with warfarin.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time. In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use. However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk. More evidence is needed to determine the safety of using garlic with warfarin.

Likelihood Possible Evidence D

Green Coffee bean extract33 drug types · 591 drugs

Ephedrine

Theoretically, concomitant use might increase the risk of stimulant adverse effects.
Coffee contains caffeine. 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. Tell patients to avoid taking caffeine with ephedrine and other stimulants.

Likelihood Probable Evidence D
Adenosine (Adenocard)

Theoretically, coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Coffee contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, 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 such as caffeine, as well as 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
Alendronate (Fosamax)

Coffee reduces alendronate bioavailability.
Separate coffee ingestion and alendronate administration by two hours. Coffee reduces alendronate bioavailability by 60%.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Coffee contains caffeine. Caffeine is reported to have antiplatelet activity. Theoretically, the caffeine in coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Theoretically, concomitant use of large amounts of coffee might increase cardiac inotropic effects of beta-agonists.
Coffee contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Cimetidine (Tagamet)

Theoretically, cimetidine might increase the effects and adverse effects of caffeine in coffee.
Coffee contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Coffee contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Contraceptive Drugs

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in coffee.
Coffee contains caffeine. Oral contraceptive drugs can decrease caffeine clearance by 40% to 65%.

Likelihood Probable Evidence B
Dipyridamole (Persantine)

Theoretically, coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Coffee contains caffeine. Caffeine is a methylxyanthine that may inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as coffee, 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 might increase the risk of adverse effects from caffeine.
Coffee contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, concomitant use might increase the risk of hypokalemia.
Coffee contains caffeine. 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.
Coffee contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence B
Lamotrigine (Lamictal)

Coffee consumption can decrease the levels and clinical effects of lamotrigine.
A pharmacokinetic study in patients taking lamotrigine shows that consumption of coffee, both caffeinated and decaffeinated, can decrease the area under the concentration-time curve (AUC) and the peak plasma level (Cmax) of lamotrigine. Each additional cup of coffee reduced the AUC and Cmax by 4% and 3%, respectively. It is unclear whether this interaction is due to induction of lamotrigine metabolism or inhibition of lamotrigine absorption.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Coffee can reduce the absorption of levothyroxine.
In some patients, coffee can reduce levothyroxine absorption, possibly through the formation of non-absorbable complexes. A pharmacokinetic study in these patients found that 25-30 mL of espresso coffee consumed with levothyroxine tablets delayed the time to peak plasma levels by 38-43 minutes, reduced the peak plasma level (Cmax) by 19% to 36%, and reduced the area under the curve (AUC) by 27% to 36%. Coffee consumed one hour after levothyroxine did not affect absorption. It is not known whether this interaction occurs with other types of coffee. Tell patients to avoid drinking coffee at the same time that they take their levothyroxine, and for up to an hour afterwards.

Likelihood Possible Evidence B
Lithium

Theoretically, abrupt coffee withdrawal might increase the levels and adverse effects of lithium.
Coffee contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels. Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported. There is also one case of a 2.8-fold increase in blood lithium levels after a patient taking lithium reduced his coffee consumption from 13-20 cups daily to 10 cups daily.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Coffee contains caffeine. 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.
Coffee contains caffeine. 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, coffee might reduce the effects of pentobarbital.
Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Coffee contains 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
Pioglitazone (Actos)

Theoretically, coffee might increase the levels and clinical effects of pioglitazone.
Coffee contains caffeine. 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.
Coffee contains caffeine. Concomitant use of caffeine and quinolones can decrease caffeine clearance and increase effects and risk of adverse effects.

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Coffee contains caffeine. 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, coffee might increase the levels and adverse effects of theophylline.
Coffee contains caffeine, which can increase theophylline levels.

Likelihood Probable Evidence B

L-Theanine3 drug types · 565 drugs

Antihypertensive Drugs

Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals. Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression. In one clinical study, some subjects taking oral theanine reported drowsiness.

Likelihood Unlikely Evidence D
Serotonergic Drugs

Clinical studies regarding the effects of L-theanine on serotonin levels are conflicting. Some studies suggest it can increase serotonin levels in the brain while others report that it may decrease them. Nevertheless, there have been no reports of l-theanine being a causative agent in serotonergic-related side effects or serotonin syndrome.

Likelihood Unlikely Evidence C

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B

Potassium3 drug types · 62 drugs

Ace Inhibitors (Aceis)

Using ACEIs with high doses of potassium increases the risk of hyperkalemia.
ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Likelihood Likely Evidence C
Angiotensin Receptor Blockers (Arbs)

Using ARBs with high doses of potassium increases the risk of hyperkalemia.
ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Likelihood Likely Evidence C
Potassium-Sparing Diuretics

Concomitant use increases the risk of hyperkalemia.
Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia.

Likelihood Likely Evidence C
The maker

Brand information

Manufacturer and brand details for Ortho Heart, from the product label.

AOR Advanced Orthomolecular Research Advanced

See all AOR Advanced Orthomolecular Research Advanced products
Name
AOR Inc.
Street Address
30 Industrial West
City
Clifton
State
NJ
ZipCode
07012
Phone Number
1-866-215-0450
Pharmacist Counseling Corner

Ortho Heart by AOR Advanced Orthomolecular Research Advanced: Common Questions

Does Ortho Heart by AOR Advanced Orthomolecular Research Advanced interact with any medications?
Yes. Based on its ingredients, Ortho Heart has a known interaction with 1,428 medications, including 10 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Ortho Heart contains 7 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Does this product have caffeine, and how much?
Yes, Ortho Heart contains caffeine. The product facts don't specify the exact dose, so check the label or contact the manufacturer for the amount per capsule.
Is it safe to take if I'm pregnant?
Avoid high-dose vitamin C supplements during pregnancy. L-theanine and hibiscus don't have enough safety data either, so it's best to avoid them in medicinal amounts. Potassium from food is fine. Talk with your doctor before taking this product while pregnant to see if it's right for you.
What is L-theanine and what does it do?
L-theanine is an amino acid that may support cognitive function, though evidence is limited. It's possibly effective for cognitive support but there isn't enough data to rate it for age-related memory loss, Alzheimer disease, anxiety, or OCD.
Can I take this if I'm on blood pressure medication?
Not without checking first. The hibiscus and potassium in this product can lower blood pressure, and L-theanine may too. Combined with your blood pressure drug, this could cause your blood pressure to drop too low. Talk with your doctor or pharmacist before starting.
Will this help my heart?
Hibiscus is possibly effective for high blood pressure, which supports heart health, but we don't have effectiveness data showing this product as a whole works for heart disease or other specific heart conditions. Talk with your doctor about whether it fits your health plan.
What are the inactive ingredients?
The inactive ingredients are microcrystalline cellulose, a capsule, silicon dioxide, sodium stearyl fumarate, and maltodextrin. These are fillers, binders, and capsule material.

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

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Ortho Heart label
Go deeper

The Full Monographs Behind Ortho Heart’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph →
Herb & supplement monograph

Garlic

Interacts with 989 drugs

Garlic is a common food and supplement that may modestly help with blood pressure and cholesterol, though the evidence is mixed and effects are usually small. It is generally safe in food am...

Read the full Garlic monograph →
Herb & supplement monograph

Coffee

Interacts with 591 drugs

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is gen...

Read the full Coffee monograph →
Herb & supplement monograph

Caffeine

Interacts with 655 drugs

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 muc...

Read the full Caffeine monograph →
Herb & supplement monograph

Potassium

Interacts with 62 drugs

Potassium is an essential mineral your body needs for nerve signals, muscle function, and a steady heartbeat, and most people get enough from a balanced diet rich in fruits and vegetables. P...

Read the full Potassium monograph →
Herb & supplement monograph

Theanine

Interacts with 565 drugs

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong drowsiness. Early research suggests it may...

Read the full Theanine monograph →
Herb & supplement monograph

Hibiscus Sabdariffa

Interacts with 1,087 drugs

Hibiscus sabdariffa is a tart, cranberry-flavored plant most often consumed as a tea, and its best-studied use is for mildly lowering blood pressure. Evidence for other uses is limited, and...

Read the full Hibiscus Sabdariffa monograph →
Sources

Sources & How We Checked

Ortho Heart's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 653 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C monograph →

Caffeine 236 references
  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
  16. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  17. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  18. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  19. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  20. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  21. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  22. 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. DOI
  23. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  24. 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. PubMed
  25. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  26. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  27. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  28. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  29. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  30. 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. PubMed
  31. Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. Ann Pharmacother 2002;36:992-5.. PubMed
  32. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  33. 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. PubMed
  34. 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.. PubMed
  35. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  36. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  37. Dreher HM. The effect of caffeine reduction on sleep quality and well-being in persons with HIV. J Psychosom Res 2003;54:191-8.. PubMed
  38. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  39. Schechter MD, Timmons GD. Objectively measured hyperactivity--II. Caffeine and amphetamine effects. J Clin Pharmacol 1985;25:276-80.. PubMed
  40. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  41. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  42. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  43. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  44. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  45. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  46. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  47. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  48. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  49. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  50. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  51. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  52. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  53. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  54. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  55. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  56. 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. PubMed
  57. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  58. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  59. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  60. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  61. 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. PubMed
  62. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  63. Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R., and Estabrook, R. W. Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25(11):1298-1303.
  64. Staib, A. H., Stille, W., Dietlein, G., Shah, P. M., Harder, S., Mieke, S., and Beer, C. Interaction between quinolones and caffeine. Drugs 1987;34 Suppl 1:170-174. PubMed
  65. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  66. Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., Chu, D. T., Pernet, A. G., Mahr, G., Sanz, F., and . Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isof
  67. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  68. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  69. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  70. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i
  71. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed
  72. Vaz, J., Kulkarni, C., David, J., and Joseph, T. Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers. Indian J.Exp.Biol. 1998;36(1):112-114.
  73. Gasior, M., Swiader, M., Przybylko, M., Borowicz, K., Turski, W. A., Kleinrok, Z., and Czuczwar, S. J. Felbamate demonstrates low propensity for interaction with methylxanthines and Ca2+ channel modulators against experimental seizures in mice. Eur.J Phar PubMed
  74. Balogh, A., Klinger, G., Henschel, L., Borner, A., Vollanth, R., and Kuhnz, W. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur.J.Clin.Pharmacol. 1995;48(2):161-166. PubMed
  75. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.
  76. Mays, D. C., Camisa, C., Cheney, P., Pacula, C. M., Nawoot, S., and Gerber, N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin.Pharmacol.Ther. 1987;42(6):621-626. PubMed
  77. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  78. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  79. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  80. 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. PubMed
  81. 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(
  82. 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. PubMed
  83. 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. PubMed
  84. 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. PubMed
  85. 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. PubMed
  86. Davis, R. H. Does caffeine ingestion affect intraocular pressure?. Ophthalmology 1989;96(11):1680-1681. PubMed
  87. 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.
  88. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
  89. 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.
  90. Lane, J. D. and Williams, R. B., Jr. Cardiovascular effects of caffeine and stress in regular coffee drinkers. Psychophysiology 1987;24(2):157-164. PubMed
  91. 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. PubMed
  92. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
  93. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775. PubMed
  94. 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. PubMed
  95. Sung, B. H., Whitsett, T. L., Lovallo, W. R., al'Absi, M., Pincomb, G. A., and Wilson, M. F. Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men. Am.J Hypertens. 1994;7(8):755-758. PubMed
  96. 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.
  97. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  98. 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. PubMed
  99. Lane, J. D. and Phillips-Bute, B. G. Caffeine deprivation affects vigilance performance and mood. Physiol Behav. 1998;65(1):171-175. PubMed
  100. 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. PubMed
  101. 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.
  102. 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. PubMed
  103. 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. PubMed
  104. 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. PubMed
  105. 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. PubMed
  106. 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. PubMed
  107. 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. PubMed
  108. Noordzij, M., Uiterwaal, C. S., Arends, L. R., Kok, F. J., Grobbee, D. E., and Geleijnse, J. M. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens. 2005;23(5):921-928. PubMed
  109. 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. PubMed
  110. Morgan, J. C. and Sethi, K. D. Drug-induced tremors. Lancet Neurol. 2005;4(12):866-876. PubMed
  111. 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.
  112. 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 PubMed
  113. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  114. Mort, J. R. and Kruse, H. R. Timing of blood pressure measurement related to caffeine consumption. Ann Pharmacother. 2008;42(1):105-110.
  115. 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. PubMed
  116. 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 PubMed
  117. 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. PubMed
  118. 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. PubMed
  119. 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. PubMed
  120. 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. PubMed
  121. 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. PubMed
  122. 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. PubMed
  123. 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. PubMed
  124. 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. PubMed
  125. 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. PubMed
  126. 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. PubMed
  127. 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.
  128. 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. PubMed
  129. Urade, Y. [Molecular mechanisms of insomnia]. Nippon Rinsho 2009;67(8):1489-1493.
  130. 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. PubMed
  131. 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. PubMed
  132. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  133. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  134. Chroscinska-Krawczyk, M., Ratnaraj, N., Patsalos, P. N., and Czuczwar, S. J. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61(5):819 PubMed
  135. Attwood, A., Terry, P., and Higgs, S. Conditioned effects of caffeine on performance in humans. Physiol Behav 3-3-2010;99(3):286-293. PubMed
  136. 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. PubMed
  137. 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. PubMed
  138. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  139. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  140. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  141. 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
  142. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  143. 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. PubMed
  144. Digdon, N. L. Circadian preference and college students' beliefs about sleep education. Chronobiol.Int 2010;27(2):297-317. PubMed
  145. 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. PubMed
  146. Casiglia, E., Bongiovi, S., Paleari, C. D., Petucco, S., Boni, M., Colangeli, G., Penzo, M., and Pessina, A. C. Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study. J.Intern.Med. 1991;229(6):501-504. PubMed
  147. Aguggia, M. and Saracco, M. G. Pathophysiology of migraine chronification. Neurol.Sci 2010;31 Suppl 1:S15-S17. PubMed
  148. Torelli, P. and Manzoni, G. C. Fasting headache. Curr Pain Headache Rep. 2010;14(4):284-291.
  149. Farag, N. H., Whitsett, T. L., McKey, B. S., Wilson, M. F., Vincent, A. S., Everson-Rose, S. A., and Lovallo, W. R. Caffeine and blood pressure response: sex, age, and hormonal status. J Womens Health (Larchmt.) 2010;19(6):1171-1176. PubMed
  150. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  151. 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.
  152. 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. PubMed
  153. 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. PubMed
  154. 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. PubMed
  155. 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 PubMed
  156. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  157. 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. PubMed
  158. 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. PubMed
  159. 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. PubMed
  160. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  161. Knight, J. M., Avery, E. F., Janssen, I., and Powell, L. H. Cortisol and depressive symptoms in a population-based cohort of midlife women. Psychosom.Med. 2010;72(9):855-861. PubMed
  162. Porkka-Heiskanen, T. Methylxanthines and sleep. Handb.Exp.Pharmacol 2011;(200):331-348. PubMed
  163. 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. PubMed
  164. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  165. 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
  166. 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. PubMed
  167. 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. PubMed
  168. Kivity, S., Ben Aharon, Y., Man, A., and Topilsky, M. The effect of caffeine on exercise-induced bronchoconstriction. Chest 1990;97(5):1083-1085. PubMed
  169. Lubin, F. and Ron, E. Consumption of methylxanthine-containing beverages and the risk of breast cancer. Cancer Lett. 1990;53(2-3):81-90. PubMed
  170. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  171. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  172. Birkett, N. J. and Logan, A. G. Caffeine-containing beverages and the prevalence of hypertension. J Hypertens.Suppl 1988;6(4):S620-S622. PubMed
  173. Fraumeni, J. F., Jr., Scotto, J., and Dunham, L. J. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204. PubMed
  174. Greden, J. F. Anxiety or caffeinism: a diagnostic dilemma. Am J Psychiatry 1974;131(10):1089-1092. PubMed
  175. 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. PubMed
  176. Firestone, P., Poitras-Wright, H., and Douglas, V. The effects of caffeine on hyperactive children. J.Learn.Disabil. 1978;11(3):133-141. PubMed
  177. 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. DOI
  178. 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. PubMed
  179. Cohen, S. Pathogenesis of coffee-induced gastrointestinal symptoms. N.Engl.J Med 7-17-1980;303(3):122-124. PubMed
  180. Feldman, M. and Barnett, C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterology 1995;108(1):125-131. PubMed
  181. 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. PubMed
  182. 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. PubMed
  183. Kaminsky, L. A., Martin, C. A., and Whaley, M. H. Caffeine consumption habits do not influence the exercise blood pressure response following caffeine ingestion. J.Sports Med.Phys.Fitness 1998;38(1):53-58.
  184. McManamy, M. C. and Schube, P. G. Caffeine intoxication: report of a case the symptoms of which amounted to a psychosis. New England Journal of Medicine 1936;215:616-620. DOI
  185. Richter, J. E., Katz, P. O., and Waring, J. P. Gastroesophageal Reflux Disease. IFFGD 2000;
  186. 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. PubMed
  187. Luebbe, A. M. Child and Adolescent Anxiety Sensitivity, Perceived Subjective Effects of Caffeine and Caffeine Consumption. J Caffeine Res 2011;1(4):213-218. DOI
  188. Li-Neng, Y., Greenstadt, L., and Shapiro, D. Effects of caffeine on blood pressure:A cross-cultural comparison. Psychophysiology 1983;20
  189. Fotherby, M. D., Ghandi, C., Haigh, R. A., Macdonald, T. A., and Potter, J. F. Sustained caffeine use has no pressor effect in the elderly. Cardiology in the Elderly 1994;2(6):499-503.
  190. 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. PubMed
  191. 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. PubMed
  192. 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 PubMed
  193. 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 PubMed
  194. 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 PubMed
  195. 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. PubMed
  196. 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. PubMed
  197. 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. PubMed
  198. 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. PubMed
  199. 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. PubMed
  200. 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
  201. Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonnière B, Romon-Rousseaux M, Buée L, Destée A, Godefroy O, Dürr A, Landwehrmeyer B;
  202. Szpak A, Allen D. A case of acute suicidality following excessive caffeine intake. J Psychopharmacol. 2012 Nov;26(11):1502-10. doi: 10.1177/0269881112442788. Epub 2012 2. PubMed
  203. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  204. 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. PubMed
  205. 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. PubMed
  206. 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. PubMed
  207. 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. PubMed
  208. 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. PubMed
  209. 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. PubMed
  210. 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.
  211. 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. PubMed
  212. 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 DOI
  213. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  214. Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015 Jul;30(4):179-82. PubMed
  215. 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. PubMed
  216. 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. PubMed
  217. 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. PubMed
  218. 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. PubMed
  219. 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. PubMed
  220. 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. PubMed
  221. 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. PubMed
  222. Zhang H, Lee ZX, Qiu A. Caffeine intake and cognitive functions in children. Psychopharmacology (Berl). 2020;237(10):3109-3116. PubMed
  223. 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 PubMed
  224. 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. PubMed
  225. 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. PubMed
  226. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  227. Hinkle SN, Gleason JL, Yisahak SF, et al. Assessment of Caffeine Consumption and Maternal Cardiometabolic Pregnancy Complications. JAMA Netw Open 2021;4(11):e2133401. PubMed
  228. Yartsev A, Peisah C. Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report. BMC Psychiatry 2021;21(1):192. PubMed
  229. Tinawi M. Severe Rhabdomyolysis Due to Strenuous Exercise With a Potential Role of a High-Caffeine Energy Drink. Cureus 2022;14(1):e20867. PubMed
  230. 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. PubMed
  231. 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. PubMed
  232. 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. PubMed
  233. Abbas-Hashemi SA, Hosseininasab D, Rastgoo S, Shiraseb F, Asbaghi O. The effects of caffeine supplementation on blood pressure in adults: A systematic review and dose-response meta-analysis. Clin Nutr ESPEN 2023;58:165-177. PubMed
  234. 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. PubMed
  235. Kühne T, Wallace E, Herzig D, et al. Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over tr
  236. Song JJ, Eyabi JC, Awatramani PD, Mitchell BG, Nene SY. Sudden Reduction in Caffeine Intake Increases Serum Lithium Concentration to Supratherapeutic Level: A Case Report. Prim Care Companion CNS Disord 2024;26(2):23cr03642. PubMed

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Garlic 154 references
  1. Silagy CA, Neil HA. A meta-analysis of the effect of garlic on blood pressure. J Hypertens 1994;12:463-8. DOI
  2. McMahon FG, Vargas R. Can garlic lower blood pressure? A pilot study. Pharmacotherapy 1993;13:406-7. DOI
  3. Auer W, Eiber A, Hertkorn E, et al. Hypertension and hyperlipidaemia: garlic helps in mild cases. Br J Clin Pract Suppl 1990;69:3-6.
  4. Garty BZ. Garlic burns. Pediatrics 1993;91:658-9.
  5. Rose KD, Croissant PD, Parliament CF, Levin MB. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurg 1990;26:880-2. PubMed
  6. Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast Reconstr Surg 1995;95:213.
  7. Sunter WH. Warfarin and garlic. Pharm J 1991;246:722.
  8. Berthold HK, Sudhop T, von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism. JAMA 1998;279:1900-2.
  9. Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr 1996;64:866-70. PubMed
  10. Steiner M, Lin RS. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J Cardiovasc Pharmacol 1998;31:904-8. PubMed
  11. Gwilt PR, Lear CL, Tempero MA, et al. The effect of garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomarkers Prev 1994;3:155-60.
  12. Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr 2000;130:2662-5. PubMed
  13. Bloch AS. Pushing the Envelope of Nutrition Support: Complementary Therapies. Nutrition 2000;16:236-9. PubMed
  14. Steiner M, Li W. Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. J Nutr 2001;131:980S-4S. PubMed
  15. Mader FH. Treatment of hyperlipidaemia with garlic-powder tablets. Evidence from the German Association of General Practitioners' multicentric placebo-controlled double-blind study. Arzneimittelforschung 1990;40:1111-6.
  16. Vorberg G, Schneider B. Therapy with garlic: results of a placebo-controlled, double-blind study. Br J Clin Pract Symp Suppl 1990;69:7-11.
  17. Simons LA, Balasubramaniam S, von Konigsmark M, et al. On the effect of garlic on plasma lipids and lipoproteins in mild hypercholesterolaemia. Atherosclerosis 1995;113:219-25. PubMed
  18. Neil HA, Silagy CA, Lancaster T, et al. Garlic powder in the treatment of moderate hyperlipidaemia: a controlled trial and meta-analysis. J R Coll Physicians Lond 1996;30:329-34. DOI
  19. Koscielny J, Klussendorf D, Latza R, et al. The antiatherosclerotic effect of Allium sativum. Atherosclerosis 1999;144:237-49. PubMed
  20. Kiesewetter H, Jung F, Jung EM, et al. Effects of garlic coated tablets in peripheral arterial occlusive disease. Clin Investig 1993;71:383-6. PubMed
  21. Kiesewetter H, Jung F, Jung EM, et al. Effect of garlic on platelet aggregation in patients with increased risk of juvenile ischaemic attack. Eur J Clin Pharmacol 1993;45:333-6. PubMed
  22. Legnani C, Frascaro M, Guazzaloca G, et al. Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. Arzneimittelforschung 1993;43:119-22.
  23. Mennella JA, Johnson A, Beauchamp GK. Garlic ingestion by pregnant women alters the odor of amniotic fluid. Chem Senses 1995;20:207-9. PubMed
  24. Mennella JA, Beauchamp GK. Maternal diet alters the sensory qualities of human milk and the nursling's behavior. Pediatrics 1991;88:737-44. DOI
  25. Mennella JA, Beauchamp GK. The effects of repeated exposure to garlic-flavored milk on the nursling's behavior. Pediatr Res 1993;34:805-8. PubMed
  26. Cronin E. Dermatitis of the hands in caterers. Contact Dermatitis 1987;17:265-9. PubMed
  27. Lee TY, Lam TH. Contact dermatitis due to topical treatment with garlic in Hong Kong. Contact Dermatitis 1991;24:193-6. PubMed
  28. Bruynzeel DP. Bulb dermatitis. Dermatological problems in the flower bulb industries. Contact Dermatitis 1997;37:70-7.
  29. Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia: a meta-analysis of randomized clinical trials. Ann Intern Med 2000;133:420-9. PubMed
  30. Ackermann RT, Mulrow CD, Ramirez G, et al. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813-24. PubMed
  31. Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002;34:234-8. PubMed
  32. Ziaei S, Hantoshzadeh S, Rezasoltani P, Lamyian M. The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia. Eur J Obstet Gynecol Reprod Biol 2001;99:201-6.. PubMed
  33. Markowitz JS, Devane CL, Chavin KD, et al. Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther 2003;74:170-7.. PubMed
  34. Josling P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Adv Ther 2001;18:189-93. PubMed
  35. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  36. Farnsworth N, Bingel A, Cordell G, et al. Potential value of plants as sources of new antifertility agents I. J Pharm Sci 1975;64:535-98. DOI
  37. Carden SM, Good WV, Carden PA, Good RM. Garlic and the strabismus surgeon. Clin Experiment Ophthalmol 2002;30:303-4. PubMed
  38. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. PubMed
  39. Dehghani F, Merat A, Panjehshahin MR, Handjani F. Healing effect of garlic extract on warts and corns. Int J Dermatol 2005;44:612-5. PubMed
  40. Dhamija P, Malhotra S, Pandhi P. Effect of oral administration of crude aqueous extract of garlic on pharmacokinetic parameters of isoniazid and rifampicin in rabbits. Pharmacology 2006;77:100-4. PubMed
  41. Macan H, Uykimpang R, Alconcel M, et al. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr 2006;136(3 Suppl):793S-795S. PubMed
  42. Hubbard VG, Goldsmith P. Garlic-fingered chefs. Contact Dermatitis 2005;52:165-6. PubMed
  43. Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008;154:1691-700. PubMed
  44. Ried K, Frank OR, Stocks NP, et al. Effect of garlic on blood pressure: A systematic review and meta-analysis. BMC Cardiovasc Disord 2008;8:13. PubMed
  45. Cox MC, Low J, Lee J, et al. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res 2006;12:4636-40.
  46. van der Walt, A., Lopata, A. L., Nieuwenhuizen, N. E., and Jeebhay, M. F. Work-related allergy and asthma in spice mill workers - The impact of processing dried spices on IgE reactivity patterns. Int Arch.Allergy Immunol. 2010;152(3):271-278. PubMed
  47. Huang, J., Frohlich, J., and Ignaszewski, A. P. The impact of dietary changes and dietary supplements on lipid profile. Can J Cardiol 2011;27(4):488-505. PubMed
  48. Hasani-Ranjbar, S., Nayebi, N., Moradi, L., Mehri, A., Larijani, B., and Abdollahi, M. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr.Pharm.Des 2010;16(26):2935-2947. PubMed
  49. Eming, S. A., Piontek, J. O., Hunzelmann, N., Rasokat, H., and Scharffetter-Kachanek, K. Severe toxic contact dermatitis caused by garlic. Br J Dermatol. 1999;141(2):391-392. PubMed
  50. Seuri, M., Taivanen, A., Ruoppi, P., and Tukiainen, H. Three cases of occupational asthma and rhinitis caused by garlic. Clin Exp.Allergy 1993;23(12):1011-1014. PubMed
  51. Rafaat, M. and Leung, A. K. Garlic burns. Pediatr Dermatol. 2000;17(6):475-476.
  52. Vaes, L. P. and Chyka, P. A. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Ann Pharmacother 2000;34(12):1478-1482. PubMed
  53. Hviid, K. and Alsbjorn, B. ["Burns" caused by local application of garlic]. Ugeskr.Laeger 12-11-2000;162(50):6853-6854.
  54. Baruchin, A. M., Sagi, A., Yoffe, B., and Ronen, M. Garlic burns. Burns 2001;27(7):781-782.
  55. Pereira, F., Hatia, M., and Cardoso, J. Systemic contact dermatitis from diallyl disulfide. Contact Dermatitis 2002;46(2):124. PubMed
  56. Hughes, T. M., Varma, S., and Stone, N. M. Occupational contact dermatitis from a garlic and herb mixture. Contact Dermatitis 2002;47(1):48. PubMed
  57. Dillon, S. A., Burmi, R. S., Lowe, G. M., Billington, D., and Rahman, K. Antioxidant properties of aged garlic extract: an in vitro study incorporating human low density lipoprotein. Life Sci. 2-21-2003;72(14):1583-1594. PubMed
  58. Groppo, F. C., Ramacciato, J. C., Simoes, R. P., Florio, F. M., and Sartoratto, A. Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against oral microorganisms. Int.Dent.J. 2002;52(6):433-437. PubMed
  59. Lachter, J., Babich, J. P., Brookman, J. C., and Factor, A. Y. Garlic: a way out of work. Mil.Med 2003;168(6):499-500. DOI
  60. Hjorth, N. and Roed-Petersen, J. Occupational protein contact dermatitis in food handlers. Contact Dermatitis 1976;2(1):28-42. PubMed
  61. van Ketel, W. G. and de Haan, P. Occupational eczema from garlic and onion. Contact Dermatitis 1978;4(1):53-54. PubMed
  62. McFadden, J. P., White, I. R., and Rycroft, R. J. Allergic contact dermatitis from garlic. Contact Dermatitis 1992;27(5):333-334. PubMed
  63. Tanamai, J., Veeramanomai, S., and Indrakosas, N. The efficacy of cholesterol-lowering action and side effects of garlic enteric coated tablets in man. J Med Assoc.Thai. 2004;87(10):1156-1161.
  64. Ashraf, R., Aamir, K., Shaikh, A. R., and Ahmed, T. Effects of garlic on dyslipidemia in patients with type 2 diabetes mellitus. J Ayub.Med Coll.Abbottabad. 2005;17(3):60-64.
  65. Laing, M. E., Barry, J., Buckley, A. M., and Murphy, G. M. Immediate and delayed hypersensitivity reactions to food and latex in a chef. Contact Dermatitis 2006;55(3):193-194. PubMed
  66. Friedman, T., Shalom, A., and Westreich, M. Self-inflicted garlic burns: our experience and literature review. Int.J Dermatol. 2006;45(10):1161-1163. PubMed
  67. van Doorn, M. B., Espirito Santo, S. M., Meijer, P., Kamerling, I. M., Schoemaker, R. C., Dirsch, V., Vollmar, A., Haffner, T., Gebhardt, R., Cohen, A. F., Princen, H. M., and Burggraaf, J. Effect of garlic powder on C-reactive protein and plasma lipids
  68. Ekeowa-Anderson, A. L., Shergill, B., and Goldsmith, P. Allergic contact cheilitis to garlic. Contact Dermatitis 2007;56(3):174-175. PubMed
  69. Gadkari JV, Joshi VD. Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects. J Postgrad.Med 1991;37:128-131.
  70. McFadden, J. P., White, J. M., Basketter, D. A., and Kimber, I. Reduced allergy rates in atopic eczema to contact allergens used in both skin products and foods: atopy and the 'hapten-atopy hypothesis'. Contact Dermatitis 2008;58(3):156-158. PubMed
  71. Lembo, G., Balato, N., Patruno, C., Auricchio, L., and Ayala, F. Allergic contact dermatitis due to garlic (Allium sativum). Contact Dermatitis 1991;25(5):330-331.
  72. Bordel-Gomez, M. T. and Miranda-Romero, A. Sensitivity to diallyl disulfide in a Spanish population. Contact Dermatitis 2008;59(2):125-126. PubMed
  73. Reinhart, K. M., Coleman, C. I., Teevan, C., Vachhani, P., and White, C. M. Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis. Ann.Pharmacother. 2008;42(12):1766-1771. PubMed
  74. Bagga, S., Thomas, B. S., and Bhat, M. Garlic burn as self-inflicted mucosal injury--a case report and review of the literature. Quintessence.Int. 2008;39(6):491-494.
  75. Shakeel, M., Trinidade, A., McCluney, N., and Clive, B. Complementary and alternative medicine in epistaxis: a point worth considering during the patient's history. Eur.J.Emerg.Med. 2010;17(1):17-19. PubMed
  76. Smyth, A. R., Cifelli, P. M., Ortori, C. A., Righetti, K., Lewis, S., Erskine, P., Holland, E. D., Givskov, M., Williams, P., Camara, M., Barrett, D. A., and Knox, A. Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis--a p
  77. Russell, J. E. Chinese complementary therapy for stress causing bilateral chemical burns to the feet. Emerg.Med.J. 2010;27(10):787. PubMed
  78. Adachi, A. [Two cases of eosinophilic gastroenteritis whose causative allergens are usefully diagnosed by patch test]. Arerugi 2010;59(5):545-551.
  79. Ried, K., Frank, O. R., and Stocks, N. P. Aged garlic extract lowers blood pressure in patients with treated but uncontrolled hypertension: a randomised controlled trial. Maturitas 2010;67(2):144-150. PubMed
  80. Hansanugrum, A. and Barringer, S. A. Effect of milk on the deodorization of malodorous breath after garlic ingestion. J.Food Sci. 8-1-2010;75(6):C549-C558. PubMed
  81. Hurley, M. N., Forrester, D. L., and Smyth, A. R. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane.Database.Syst.Rev. 2010;(10):CD008037. PubMed
  82. Nahas, R. and Balla, A. Complementary and alternative medicine for prevention and treatment of the common cold. Can.Fam.Physician 2011;57(1):31-36.
  83. Takeuchi, S., Matsuzaki, Y., Ikenaga, S., Nishikawa, Y., Kimura, K., Nakano, H., and Sawamura, D. Garlic-induced irritant contact dermatitis mimicking nail psoriasis. J.Dermatol. 2011;38(3):280-282. PubMed
  84. Davis, L. E., Shen, J. K., and Cai, Y. Antifungal activity in human cerebrospinal fluid and plasma after intravenous administration of Allium sativum. Antimicrob.Agents Chemother. 1990;34(4):651-653. PubMed
  85. Ashraf, R., Khan, R. A., and Ashraf, I. Garlic (Allium sativum) supplementation with standard antidiabetic agent provides better diabetic control in type 2 diabetes patients. Pak.J.Pharm.Sci. 2011;24(4):565-570.
  86. Bakhshi, M., Taheri, J. B., Shabestari, S. B., Tanik, A., and Pahlevan, R. Comparison of therapeutic effect of aqueous extract of garlic and nystatin mouthwash in denture stomatitis. Gerodontology. 2012;29(2):e680-e684. PubMed
  87. Kianoush, S., Balali-Mood, M., Mousavi, S. R., Moradi, V., Sadeghi, M., Dadpour, B., Rajabi, O., and Shakeri, M. T. Comparison of therapeutic effects of garlic and d-Penicillamine in patients with chronic occupational lead poisoning. Basic Clin.Pharmacol
  88. Filobbos, G., Chapman, T., and Gesakis, K. Iatrogenic burns from garlic. J.Burn Care Res. 2012;33(1):e21. PubMed
  89. Nantz, M. P., Rowe, C. A., Muller, C. E., Creasy, R. A., Stanilka, J. M., and Percival, S. S. Supplementation with aged garlic extract improves both NK and gammadelta-T cell function and reduces the severity of cold and flu symptoms: a randomized, double
  90. Fedder, S. L. Spinal epidural hematoma and garlic ingestion. Neurosurgery 1990;27(4):659. DOI
  91. Lissiman, E., Bhasale, A. L., and Cohen, M. Garlic for the common cold. Cochrane.Database.Syst.Rev. 2012;3:CD006206. PubMed
  92. Kaplan, B., Schewach-Millet, M., and Yorav, S. Factitial dermatitis induced by application of garlic. Int J Dermatol. 1990;29(1):75-76. PubMed
  93. Harenberg, J., Giese, C., and Zimmermann, R. Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggregation and serum cholesterol levels in patients with hyperlipoproteinemia. Atherosclerosis 1988;74(3):247-249. PubMed
  94. Parish, R. A., McIntire, S., and Heimbach, D. M. Garlic burns: a naturopathic remedy gone awry. Pediatr.Emerg.Care 1987;3(4):258-260.
  95. Bojs, G. and Svensson, A. Contact allergy to garlic used for wound healing. Contact Dermatitis 1988;18(3):179-181. PubMed
  96. Bleumink, E. and Nater, J. P. Contact dermatitis to garlic; crossreactivity between garlic, onion and tulip. Arch.Dermatol.Forsch 8-15-1973;247(2):117-124. PubMed
  97. Yoshikawa, K., Hadame, K., Saitoh, K., and Hijikata, T. Patch tests with common vegetables in hand dermatitis patients. Contact Dermatitis 1979;5(4):274-275. PubMed
  98. Bleumink, E., Doeglas, H. M., Klokke, A. H., and Nater, J. P. Allergic contact dermatitis to garlic. Br.J Dermatol. 1972;87(1):6-9. PubMed
  99. Papageorgiou, C., Corbet, J. P., Menezes-Brandao, F., Pecegueiro, M., and Benezra, C. Allergic contact dermatitis to garlic (Allium sativum L.). Identification of the allergens: the role of mono-, di-, and trisulfides present in garlic. A comparative stu DOI
  100. anonymous. Garlic in cryptococcal meningitis: a preliminary report of 21 cases. Chin Med J (Engl.) 1980;93(2):123-126.
  101. Szybejko, J., Zukowski, A., and Herbec, R. [Unusual cause of obturation of the small intestine]. Wiad.Lek. 4-15-1982;35(2):163-164.
  102. Mitchell, J. C. Contact sensitivity to garlic (Allium). Contact Dermatitis 1980;6(5):356-357. PubMed
  103. German, K., Kumar, U., and Blackford, H. N. Garlic and the risk of TURP bleeding. Br J Urol 1995;76(4):518. PubMed
  104. Petry, J. J. Garlic and postoperative bleeding. Plast.Reconstr.Surg 1995;96(2):483-484. PubMed
  105. Canduela, V., Mongil, I., Carrascosa, M., Docio, S., and Cagigas, P. Garlic: always good for the health? Br J Dermatol. 1995;132(1):161-162. PubMed
  106. Farrell, A. M. and Staughton, R. C. Garlic burns mimicking herpes zoster. Lancet 4-27-1996;347(9009):1195. PubMed
  107. Delaney, T. A. and Donnelly, A. M. Garlic dermatitis. Austr J Dermatol 1996;37(2):109-110.
  108. Ruocco, V., Brenner, S., and Lombardi, M. L. A case of diet-related pemphigus. Dermatology 1996;192(4):373-374. PubMed
  109. Jain, R. C. Effect of garlic on serum lipids, coagulability and fibrinolytic activity of blood. Am J Clin Nutr 1977;30(9):1380-1381. PubMed
  110. Rance, F. and Dutau, G. Labial food challenge in children with food allergy. Pediatr Allergy Immunol. 1997;8(1):41-44. PubMed
  111. Roberge, R. J., Leckey, R., Spence, R., and Krenzelok, E. J. Garlic burns of the breast. Am J Emerg.Med 1997;15(5):548. PubMed
  112. Kumar, M. and Berwal, J. S. Sensitivity of food pathogens to garlic (Allium sativum). J Appl.Microbiol. 1998;84(2):213-215. PubMed
  113. Bimmermann A, Weingart K, and Schwartzkopff W. Allium sativum: Studie zur Wirksamkeit bei Hyperlipoproteinamie. Therapiewoche 1988;38:3885-3890.
  114. Czerny B and Samochowiec J. Klinische Untersuchungen mit einem Knoblauch-Lezithin-Präparat. Arztezeitschr Naturheilverf 1996;37:126-129.
  115. Yeh YY, Lin RI, Yeh SM, and et al. Garlic reduces plasma cholesterol in hypercholesterolemic men maintaining habitual diets. In: Ohigashi H, Osawa T, Terao J, and et al. Food Factors for Cancer Prevention. Tokyo, Japan: Springer-Verlag;1997. DOI
  116. Edelstein AJ and Johnstown PA. Dermatitis caused by garlic. Arch Dermatol 1950;61:111. PubMed
  117. Fleischer S, Bayerl C, and Jung EG. [Occupational allergic hand dermatitis to garlic in a pizza baker]. Aktuelle Dermatol 1996;22:278-279.
  118. Gaddoni G, Selvi M, Resta F, and et al. Allergic contact dermatitis to garlic in a cook. Ann Ital Dermatol Clin Sperimentale 1994;48:120-121.
  119. Ince DI, Sonmez GT, and Ince ML. Effects garlic on aerobic performance. Turkish Journal of Medical Sciences 2000;30(6):557-561.
  120. Soltani PR. Preecampisia [sic] is an important complication of pregnancy which can result in morbidity and mortality in mother, fetus and the neonate. Journal of Medical Council of Islamic Republic of Iran (J MED COUNC ISLAMIC REPUB IRAN) 2005;23(3):319.
  121. Gravas S, Tzortzis V Rountas C Melekos MD. Extracorporeal shock-wave lithotripsy and garlic consumption: a lesson to learn. Urol Res. 2010;38(1):61-63. PubMed
  122. Sunter WH. Warfarin and garlic. Pharm J 1991;246:722.
  123. Jeyaraj S, Shivaji G, and Jeyaraj SD. Effect of a combined supplementation of fish oil (MEGA-3) with garlic pearls on the serum lipid profile, blood pressure and body mass index of hypercholesterolemic subjects. Heart 2000;83(suppl 2):A4.
  124. Ashraf R, Khan RA, Ashraf I, Qureshi AA. Effects of Allium sativum (garlic) on systolic and diastolic blood pressure in patients with essential hypertension. Pak J Pharm Sci 2013;26(5):859-63.
  125. Duncan A, Mills J. An unusual case of HIV virologic failure during treatment with boosted atazanavir. AIDS 2013;27:1361-2. PubMed
  126. Ergul B, Cakal B. Dysphagia caused by garlic induced esophagitis. Clin Res Hepatol Gastroenterol 2012;36(6):e134. PubMed
  127. Karabacak E, Aydin E, Kutlu A, Dogan B. An unusual garlic burn occurring on an unexpected area. BMJ Case Rep 2014. PubMed
  128. Ma S, Yin J. Anaphylaxis induced by ingestion of raw garlic. Foodborne Pathog Dis 2012;9(8):773-5. PubMed
  129. Mane SK, Jordan PA, Bahna SL. Eosinophilic esophagitis to unsuspected rare food allergen. Ann Allergy Asthma Immunol 2013;111(1):64-5. PubMed
  130. Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr 2013;67(1):64-70. PubMed
  131. Roussos AP, Hirsch AR. Alliaceous migraines. Headache 2014;54(2):378-82. PubMed
  132. Watson CJ, Grando D, Fairley CK, et al. The effects of oral garlic on vaginal candida colony counts: a randomised placebo controlled double-blind trial. BJOG 2014;121(4):498-506. PubMed
  133. Xu S, Heller M, Wu PA, Nambudri VE. Chemical burn caused by topical application of garlic under occlusion. Dermatol Online J 2014;20(1):21261. DOI
  134. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  135. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003;55(2):199-202. PubMed
  136. Hou LQ, Liu YH, Zhang YY. Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2015;24(4):575-82.
  137. Oberle M, Wachs T, Brisson P. Garlic burn to the face. J Spec Oper Med. Winter 2016;16(4):80-81. PubMed
  138. Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: An updated meta-analysis and review. J Nutr. 2016;146(2):389S-396S. PubMed
  139. Shaikh SA, Tischer S, Choi EK, Fontana RJ. Good for the lung but bad for the liver? Garlic-induced hepatotoxicity following liver transplantation. J Clin Pharm Ther. 2017;42(5):646-648. PubMed
  140. Suzuki Y, Saito J, Misa K, Fukuhara N, Fukuhara A, Munakata M. A case of black garlic-induced pneumonia as an adverse reaction. Allergol Int. 2016;65(3):353-5. PubMed
  141. Treudler R, Reuter A, Engin AM, Simon JC. A case of anaphylaxis after garlic ingestion: Is alliinase the only culprit allergen? J Investig Allergol Clin Immunol. 2015;25(5):374-5.
  142. Woodbury A, Sniecinski R. Garlic-induced surgical bleeding: How much is too much? A Case Rep. 2016;7(12):266-269. PubMed
  143. Yagami A, Suzuki K, Sano A, et al. Immediate allergy due to raw garlic (Allium sativum L.). J Dermatol. 2015;42(10):1026-7.
  144. Gandomkar H, Mahmoodzadeh H, Tavakoli H, Fazeli M, Rezaei J. Garlic-induced esophageal perforation: A case series. Asian J Surg. 2020;43(6):696-697. PubMed
  145. Dev T, Bharti P, Patel U, Bhari N. Chronic paronychia and nail dystrophy: an atypical presentation of allergic contact dermatitis to garlic. Int J Dermatol 2021 Feb 11. doi: 10.1111/ijd.15430. PubMed
  146. Jafari F, Tabarrai M, Abbassian A, Jafari F, Ayati MH. Effect of Garlic (Allium sativum) Supplementation on Premenstrual Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial. Evid Based Complement Alternat Med 2021;2021:9965064. PubMed
  147. Tomo S, Santos IDS, Cruz TMD, Miyahara GI, Simonato LE. Garlic burn trauma of the oral mucosa in a patient with trigeminal neuralgia: A case report. Dent Traumatol 2022. PubMed
  148. Wasef AK, Wahdan SA, Saeed NM, El-Demerdash E. Effects of aged garlic and ginkgo biloba extracts on the pharmacokinetics of sofosbuvir in rats. Biopharm Drug Dispos. 2022;43(4):152-62. PubMed
  149. Sangouni AA, Alizadeh M, Jamalzehi A, Hosseinzadeh M, Parastouei K. Garlic supplementation improves intestinal transit time, lipid accumulation product and cardiometabolic indices in subjects with metabolic syndrome: A randomized controlled trial. Phytoth PubMed
  150. Taghavi MR, Tavanaei Tamanaei T, Oghazian MB, et al. Effectiveness of fortified garlic extract oral capsules as adjuvant therapy in hospitalized patients with coronavirus disease 2019: A triple-blind randomized controlled clinical trial. Curr Ther Res Cli PubMed
  151. Jamaluddin J, Jamil SN. An unexpected reaction to topical garlic medicament - A case report of irritant contact dermatitis successfully managed in primary care. Cureus 2023;15(1):e33657. PubMed
  152. Nair A, Abdelqader B, Sureshkumar S, Katmawai-Sabbagh S. Hematuria and dietary supplements - A case report on pronounced bleeding following a minimally invasive urological intervention in a patient on long term garlic supplements. Urol Case Rep 2023;50:10 PubMed
  153. Zhao X, Cheng T, Xia H, Yang Y, Wang S. Effects of Garlic on Glucose Parameters and Lipid Profile: A Systematic Review and Meta-Analysis on Randomized Controlled Trials. Nutrients 2024;16(11):1692. PubMed
  154. Bhat GS, Shastry A. Prospective, randomized, placebo-controlled, two-arm study to evaluate the efficacy of coadministration of garlic as a hydrogen sulfide donor and tadalafil in patients with erectile dysfunction not responding to tadalafil alone - A pil

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Coffee 175 references
  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. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  8. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.
  9. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  10. 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.
  11. Grubben MJ, Boers GH, Blom HJ, et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr 2000;71:480-4. PubMed
  12. 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
  13. 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
  14. 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
  15. 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.
  16. 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
  17. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  18. 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
  19. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  20. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 1999;53:831-9. PubMed
  21. Dews PB, Curtis GL, Hanford KJ, O'Brien CP. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol 1999;39:1221-32. PubMed
  22. FDA. Proposed rule: dietary supplements containing ephedrine alkaloids. Available at: www.verity.fda.gov (Accessed 25 January 2000).
  23. Margolin KA, Green MR. Polymicrobial enteric septicemia from coffee enemas. West J Med 1984;140:460.
  24. Urgert R, Vliet TV, Zock PL, et al. Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. Am J Clin Nutr 2000;72:1107-10. PubMed
  25. Green S. A critique of the rationale for cancer treatment with coffee enemas and diet. JAMA 1992;268:3224-7. DOI
  26. Shils ME, Herman MG. Unproved dietary claims in the treatment of patients with cancer. Bull N Y Acad Med 1982;58:323-39.
  27. Boozer CN, Nasser JA, Heymsfield SB, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25:316-24. PubMed
  28. Bak AA, Grobbee DE. The effect of serum cholesterol levels of coffee brewed by filtering or boiling. N Engl J Med 1989;321:1432-7.
  29. Briggs GB, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.
  30. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  31. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  32. 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. PubMed
  33. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. PubMed
  34. Sinclair CJ, Geiger JD. Caffeine use in sports. A pharmacological review. J Sports Med Phys Fitness 2000;40:71-9.
  35. Heliovaara M, Aho K, Knekt P, et al. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis 2000;59:631-5. PubMed
  36. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8. PubMed
  37. Brown BT. Treating cancer with coffee enemas and diet. JAMA 1993;269:1635-6. DOI
  38. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  39. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  40. Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. PubMed
  41. Klag MJ, Wang NY, Meoni LA, et al. Coffee intake and risk of hypertension: The John Hopkins precursors study. Arch Intern Med 2002;162:657-62. DOI
  42. Brenner H, Rothenbacher D, Bode G, Adler G. Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study. BMJ 1997;315:1489-92.
  43. Jee SH, He J, Appel LJ, et al. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2001:153:353-62. PubMed
  44. Michaud DS, Giovannucci E, Willett WC, et al. Coffee and alcohol consumption and risk of pancreatic cancer in two prospective United States cohorts. Cancer Epidemiol Biomarkers Prev 2001;10:429-37.
  45. Tavani A, Pregnolato A, La Vecchia C, et al. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev 1998;7:77-82.
  46. Tavani A, La Vecchia C. Coffee and cancer: a review of epidemiological studies, 1990-1999. Eur J Cancer Prev 2000;9:241-56.
  47. Hartman TJ, Tangrea JA, Pietinen P, et al. Tea and coffee consumption and risk of colon and rectal cancer in middle-aged Finnish men. Nutr Cancer 1998;31:41-8. PubMed
  48. Anon. Filtering the news about coffee. University of California, Berkeley Wellness Letter 2001:17:1-2.
  49. 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. PubMed
  50. Jacobsen BK, Heuch I. Coffee, K-ras mutations and pancreatic cancer: a heterogeneous aetiology or an artefact? J Epidemiol Community Health 2000;54:654-5.
  51. Porta M, Malats N, Alguacil J, et al. Coffee, pancreatic cancer, and K-ras mutations: updating the research agenda. J Epidemiol Community Health 2000;54:656-9.
  52. Kuper HE, Mucci LA, Trichopoulos D. Coffee, pancreatic cancer, and the question of causation. J Epidemiol Community Health 2000;54:650-1.
  53. Urgert R, Meyboom S, Kuilman M, et al. Comparison of effect of cafetiere and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial. BMJ 1996;313:1362-6.. DOI
  54. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
  55. 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. PubMed
  56. 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.. PubMed
  57. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003;289:1537-45.. PubMed
  58. McGowan JD, Altman RE, Kanto WP Jr. Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine. South Med J 1988;81:1092-4.. PubMed
  59. Massey LK. Is caffeine a risk factor for bone loss in the elderly? Am J Clin Nutr 2001;74:569-70. PubMed
  60. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  61. Wisborg K, Kesmodel U, Bech BH, et al. Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study. BMJ 2003;326:420.. PubMed
  62. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI
  63. Infante S, Baeza ML, Calvo M, et al. Anaphylaxis due to caffeine. Allergy 2003;58:681-2. PubMed
  64. Massey LK, Whiting SJ. Caffeine, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. PubMed
  65. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228-32. PubMed
  66. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. PubMed
  67. Food and Nutrition Board, Institute of Medicine. Nutrition during lactation. Washington, DC: National Academy Press, 1991. Available at: http://books.nap.edu/books/0309043913/html.
  68. Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995;58:288-98. PubMed
  69. May DC, Jarboe CH, VanBakel AB, Williams WM. Effects of cimetidine on caffeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982;31:656-61. PubMed
  70. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. PubMed
  71. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  72. Sanderink GJ, Bournique B, Stevens J, et al. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. Pharmacol Exp Ther 1997;282:1465-72. DOI
  73. Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989;37:279-83. PubMed
  74. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  75. Underwood DA. Which medications should be held before a pharmacologic or exercise stress test? Cleve Clin J Med 2002;69:449-50. PubMed
  76. Aqel RA, Zoghbi GJ, Trimm JR, et al. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol 2004;93:343-6. PubMed
  77. Zheng XM, Williams RC. Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. J Nucl Med Technol 2002;30:123-7.
  78. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
  79. Holmgren P, Norden-Pettersson L, Ahlner J. Caffeine fatalities--four case reports. Forensic Sci Int 2004;139:71-3. PubMed
  80. Dews PB, O'Brien CP, Bergman J. Caffeine: behavioral effects of withdrawal and related issues. Food Chem Toxicol 2002;40:1257-61. PubMed
  81. Beach CA, Mays DC, Guiler RC, et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther 1986;39:265-70. PubMed
  82. Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993;44:295-8. PubMed
  83. Baker JA, McCann SE, Reid ME, et al. Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers. Nutr Cancer 2005;52:15-21. PubMed
  84. Benowitz NL, Osterloh J, Goldschlager N, et al. Massive catecholamine release from caffeine poisoning. JAMA 1982;248:1097-8. DOI
  85. Leson CL, McGuigan MA, Bryson SM. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol 1988;26:407-15. PubMed
  86. 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. PubMed
  87. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA 2005;294:2330-5. PubMed
  88. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI
  89. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. PubMed
  90. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
  91. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045-53. PubMed
  92. Baylin A, Hernandez-Diaz S, Kabagambe EK, et al. Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction. Epidemiology 2006;17:506-11. PubMed
  93. 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. PubMed
  94. Savitz DA, Chan RL, Herring AH, et al. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. PubMed
  95. Benvenga S. Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008;18:293-301. PubMed
  96. Stille, W., Harder, S., Mieke, S., Beer, C., Shah, P. M., Frech, K., and Staib, A. H. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J.Antimicrob.Chemother. 1987;20(5):729-734. PubMed
  97. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  98. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.
  99. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  100. Azcona O, Barbanoi MJ, Torrent J, Jane F. Evaluation of the central effects of alcohol and caffeine interaction. Br J Clin Pharmacol 1995;40:393-400. PubMed
  101. Harder S, Staib AH, Beer C, et al. 4-quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol 1988;35:651-6. PubMed
  102. Zhang LL, Zhang JR, Guo K, et al. Effects of fluoroquinolones on CYP4501A and 3A in male broilers. Res Vet Sci 2011;90:99-105. PubMed
  103. Cesana M, Broccali G, Imbimbo BP, Crema A. Effect of single doses of rufloxacin on the disposition of theophylline and caffeine after single administration. Int J Clin Pharmacol Ther Toxicol 1991:29:133-8.
  104. Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol 1981;12:155-9. PubMed
  105. Smits P, Straatman C, Pijpers E, Thien T. Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine. Clin Pharmacol Ther 1991;50:529-37. PubMed
  106. Zelenitsky SA, Norman A, Nix DE. The effects of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. J Infect Dis Pharmacother 1995;1:1-11.
  107. Joeres R, Richter E. Mexiletine and caffeine elimination. N Engl J Med 1987;317:117. PubMed
  108. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991;49:248-55. PubMed
  109. Smits, P., Temme, L., and Thien, T. The cardiovascular interaction between caffeine and nicotine in humans. Clin Pharmacol Ther 1993;54(2):194-204. PubMed
  110. MacKenzie, T., Comi, R., Sluss, P., Keisari, R., Manwar, S., Kim, J., Larson, R., and Baron, J. A. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007;56(12):1694-1698. PubMed
  111. 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. PubMed
  112. 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. PubMed
  113. Hashim, H. and Al, Mousa R. Management of fluid intake in patients with overactive bladder. Curr.Urol.Rep. 2009;10(6):428-433. PubMed
  114. Moisey, L. L., Robinson, L. E., and Graham, T. E. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males. Br.J Nutr. 2010;103(6):833-841. PubMed
  115. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  116. Buscemi, S., Verga, S., Batsis, J. A., Donatelli, M., Tranchina, M. R., Belmonte, S., Mattina, A., Re, A., and Cerasola, G. Acute effects of coffee on endothelial function in healthy subjects. Eur.J Clin Nutr. 2010;64(5):483-489. PubMed
  117. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  118. Mevcha, A., Gulur, D. M., and Gillatt, D. Diagnosing urological disorders in ageing men. Practitioner 2010;254(1726):25-9, 2.
  119. Banko, L. T., Haq, S. A., Rainaldi, D. A., Klem, I., Siegler, J., Fogel, J., Sacchi, T. J., and Heitner, J. F. Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine his
  120. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  121. 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. PubMed
  122. 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 PubMed
  123. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed
  124. Gronroos, N. N. and Alonso, A. Diet and risk of atrial fibrillation - epidemiologic and clinical evidence -. Circ.J 2010;74(10):2029-2038. PubMed
  125. 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. PubMed
  126. Orozco-Gregorio, H., Mota-Rojas, D., Bonilla-Jaime, H., Trujillo-Ortega, M. E., Becerril-Herrera, M., Hernandez-Gonzalez, R., and Villanueva-Garcia, D. Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia PubMed
  127. 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
  128. Smits, P., Lenders, J. W., and Thien, T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin.Pharmacol.Ther. 1990;48(4):410-418. PubMed
  129. Rossignol, A. M. and Bonnlander, H. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome. Am.J.Public Health 1990;80(9):1106-1110. PubMed
  130. Jeppesen, U., Loft, S., Poulsen, H. E., and Brsen, K. A fluvoxamine-caffeine interaction study. Pharmacogenetics 1996;6(3):213-222. PubMed
  131. Smits, P., Corstens, F. H., Aengevaeren, W. R., Wackers, F. J., and Thien, T. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion. J Nucl.Med. 1991;32(8):1538-1541. DOI
  132. Wang Y, Yu X, Wu Y, Zhang D. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies. Lung Cancer. 2012;78(2):169-70. PubMed
  133. 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 PubMed
  134. 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. PubMed
  135. 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. PubMed
  136. 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. PubMed
  137. 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
  138. van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014 May 6;160(9):657-8. doi: 10.7326/L14-5009-8. No abstract available. PubMed
  139. 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. PubMed
  140. Turati F, Galeone C, Talamini R, et al. Coffee, decaffeinated coffee, tea, and pancreatic cancer risk: a pooled-analysis of two Italian case-control studies. Eur J Cancer Prev 2011;20(4):287-92. PubMed
  141. 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. PubMed
  142. Acosta RD, Cash BD. Clinical effects of colonic cleansing for general health promotion: a systematic review. Am J Gastroenterol. 2009;104(11):2830-6. PubMed
  143. Kunitake Y, Mizoguchi Y, Sogawa R, et al. Effect of excessive coffee consumption on the clinical course of a patient with bipolar disorder: a case report and literature review. Clin Neuropharmacol. 2017 Jul/Aug;40(4):160-162. doi: 10.1097/WNF.00000000 PubMed
  144. Crippa A, Discacciati A, Larsson SC, Wolk A, Orsini N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 2014 Oct 15;180(8):763-75. doi: 10.1093/aje/kwu194. PubMed
  145. Loftfield E, Cornelis MC, Caporaso N, Yu K, Sinha R, Freedman N. Association of coffee drinking With mortality by genetic variation in caffeine metabolism: findings from the UK biobank. JAMA Intern Med. 2018 Aug 1;178(8):1086-1097. doi: 10.1001/jamaintern PubMed
  146. 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 DOI
  147. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias: time to grind the data. JACC: Clin Electrophysiol. 2018;4(4):425-32. PubMed
  148. 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. PubMed
  149. Lee AH, Kabashneh S, Tsouvalas CP, et al. Proctocolitis from coffee enema. ACG Case Rep J. 2020;7(1):e00292. PubMed
  150. Tverdal A, Selmer R, Cohen JM, Thelle DS. Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? Eur J Prev Cardiol. 2020:2047487320914443. PubMed
  151. Yamakawa M, Wada K, Goto Y, et al. Associations between coffee consumption and all-cause and cause-specific mortality in a Japanese city: the Takayama study. Public Health Nutr. 2019;22(14):2561-2568. PubMed
  152. Zhou CD, Kuan AS, Reeves GK, et al. Coffee and pancreatic cancer risk among never-smokers in the UK prospective Million Women Study. Int J Cancer. 2019;145(6):1484-1492. PubMed
  153. 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 PubMed
  154. Ruggiero E, Di Castelnuovo A, Costanzo S, et al. Daily coffee drinking is associated with lower risks of cardiovascular and total mortality in a general Italian population: Results from the Moli-sani study. J Nutr. 2020:nxaa365. PubMed
  155. Kim Y, Je Y, Giovannucci E. Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers. Eur J Epidemiol. 2019 Aug;34(8):731-752. doi: 10.1007/s10654-019-00524-3. Epub 2019 May 4. PubMed
  156. Stevens LM, Linstead E, Hall JL, Kao DP. Association between coffee intake and incident heart failure risk: A machine learning analysis of the FHS, the ARIC Study, and the CHS. Circ Heart Fail. 2021:CIRCHEARTFAILURE119006799. PubMed
  157. Ribeiro EM, Alves M, Costa J, Ferreira JJ, Pinto FJ, Caldeira D. Safety of coffee consumption after myocardial infarction: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2020;30(12):2146-2158. PubMed
  158. Grosso G, Micek A, Godos J, ET AL. Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis. Eur J Epidemiol. 2016;31(12):1191-1205. PubMed
  159. Kim EJ, Hoffmann TJ, Nah G, Vittinghoff E, Delling F, Marcus GM. Coffee consumption and incident tachyarrhythmias: Reported behavior, mendelian randomization, and their interactions. JAMA Intern Med. 2021. PubMed
  160. Loftfield E, Freedman ND, Graubard BI, et al. Association of coffee consumption with overall and cause-specific mortality in a large US prospective cohort study. Am J Epidemiol. 2015;182(12):1010-22. PubMed
  161. Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E. The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr. 2011;94(4):1113-26. PubMed
  162. Miranda AM, Goulart AC, Benseñor IM, Lotufo PA, Marchioni DM. Moderate coffee consumption is associated with lower risk of mortality in prior Acute Coronary Syndrome patients: a prospective analysis in the ERICO cohort. Int J Food Sci Nutr. 2020:1-11.
  163. Nordestgaard AT, Nordestgaard BG. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95?000-223?000 individuals. Int J Epidemiol. 2016;45(6):1938-1952. PubMed
  164. Zhang Y, Yang H, Li S, Li WD, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med 2021;18(11):e1003830. PubMed
  165. Chan L, Hong CT, Bai CH. Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies. BMC Neurol 2021;21(1):380. PubMed
  166. Welty TE, Gidal BE, Duan J, et al. Coffee and cigarette smoking interactions with lamotrigine. Epilepsy Behav 2021;116:107741. PubMed
  167. 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. PubMed
  168. 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. PubMed
  169. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
  170. 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. PubMed
  171. Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H. Coffee and green tea consumption and cardiovascular disease mortality among people with and without hypertension. J Am Heart Assoc 2023;12(2):e026477. PubMed
  172. Han M, Oh Y, Myung SK. Coffee intake and risk of hypertension: A meta-analysis of cohort studies. J Korean Med Sci 2022;37(45):e332. PubMed
  173. Sehrawat O, Mehra NS, Kowlgi NG, et al. Association between coffee consumption and incident atrial fibrillation (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol 2023;186:5-10. PubMed
  174. Marcus GM, Rosenthal DG, Nah G, et al. Acute effects of coffee consumption on health among ambulatory adults. N Engl J Med. 2023;388(12):1092-1100. PubMed
  175. Abtan J, Ducrocq G, Elbez Y, et al. Association between coffee or tea consumption and cardiovascular outcomes in patients with stable coronary artery disease: Analysis from the CLARIFY registry. Arch Cardiovasc Dis 2023;116(8-9):382-389. PubMed

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Potassium 12 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Gennaro A. Remington: The Science and Practice of Pharmacy. 19th ed. Lippincott: Williams & Wilkins, 1996.
  3. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA 1997;277:1624-32. PubMed
  4. Phillips, C. O., Kashani, A., Ko, D. K., Francis, G., and Krumholz, H. M. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from ra DOI
  5. Altieri, P. I., Herrero, C., Suero, R., and Ortiz, A. Bleeding duodenal ulcer in a patient taking slow-releasing potassium tablets. Bol.Asoc.Med P.R. 1977;69(8):276.
  6. Raf, L. E. Enteric-coated potassium chloride tablets and ulcer of the small intestine. Acta Chir Scand Suppl 1967;(374):1-87.
  7. Potassium chloride oral solution [package insert]. Allentown, PA: Lehigh Valley Technologies, Inc.; 2014.
  8. Potassium chloride injection [package insert]. Lake Forest, IL: Hospira Inc.; 2009.
  9. Patel RB, Tannenbaum S, Viana-Tejedor A, et al. Serum potassium levels, cardiac arrhythmias, and mortality following non-ST-elevation myocardial infarction or unstable angina: insights from MERLIN-TIMI 36. Eur Heart J Acute Cardiovasc Care 2017 Feb;6(1):1 PubMed
  10. Malta D, Arcand J, Ravindran A, Floras V, Allard JP, Newton GE. Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system. Am J Clin Nutr 2016 Oct;104(4 PubMed
  11. Keskin M, Kaya A, Tatlisu MA, et al. The effect of serum potassium level on in-hospital and long-term mortality in ST elevation myocardial infarction. Int J cardiol. 2016 Oct 15;221:505-10.
  12. Stallings VA, Harrison M, Oria M; Committee to Review the Dietary Reference Intakes for Sodium and Potassium, Food and Nutrition Board, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. Washington (DC): National Acad

See these in context on the Potassium monograph →

Theanine 6 references
  1. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylethylamide in spontaneously hypertensive rats. Life Sci 1998;62:1065-8.
  2. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., and Scholey, A. B. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol.Psychol. 2008;77(2):113-122. PubMed
  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., and Takeuchi, N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci.Biotechnol.Biochem. 1995;59(4):615-618. PubMed
  4. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-
  5. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 2017;29(2):72-9.
  6. Tsuchiya T, Honda H, Oikawa M, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol 2016;21(6):1085-90. PubMed

See these in context on the Theanine monograph →

Hibiscus Sabdariffa 19 references
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  2. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on pharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet 2004;29:25-9.
  3. McKay DL, Chen CY, Saltzman E, Blumberg JB. Hibiscus Sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults. J Nutr 2010;140:298-303. PubMed
  4. Kuriyan R, Kumar DR, Rajendran R, Kurpad AV. An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial. BMC Complement Altern Med 2010;10:27. PubMed
  5. Haji, Faraji M. and Haji, Tarkhani A. The effect of sour tea (Hibiscus sabdariffa) on essential hypertension. J.Ethnopharmacol. 1999;65(3):231-236. PubMed
  6. Mozaffari-Khosravi, H., Jalali-Khanabadi, B. A., Afkhami-Ardekani, M., Fatehi, F., and Noori-Shadkam, M. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Hum.Hypertens 2009;23(1):48-54. PubMed
  7. Gurrola-Diaz, C. M., Garcia-Lopez, P. M., Sanchez-Enriquez, S., Troyo-Sanroman, R., Andrade-Gonzalez, I., and Gomez-Leyva, J. F. Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metaboli
  8. Hernandez-Perez, F. and Herrera-Arellano, A. [Therapeutic use Hibiscus sabadariffa extract in the treatment of hypercholesterolemia. A randomized clinical trial]. Rev.Med Inst.Mex.Seguro.Soc. 2011;49(5):469-480.
  9. Mahmoud, B. M., Ali, H. M., Homeida, M. M., and Bennett, J. L. Significant reduction in chloroquine bioavailability following coadministration with the Sudanese beverages Aradaib, Karkadi and Lemon. J.Antimicrob.Chemother. 1994;33(5):1005-1009.
  10. Iyare EE, Adegoke OA. Maternal consumption of an aqueous extract of Hibiscus sabdariffa during lactation accelerates postnatal weight and delays onset of puberty in female offspring. Niger J Physiol Sci. 2008 Jun-Dec;23(1-2):89-94. PubMed
  11. Johnson SS, Oyelola FT, Ari T, Juho H. In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. Afr J Tradit Complement Altern Med. 2013 Apr 12;10(3):533-40.
  12. Sabzghabaee AM, Ataei E, Kelishadi R, Ghannadi A, Soltani R, Badri S, Shirani S. Effect of Hibiscus sabdariffa Calices on Dyslipidemia in Obese Adolescents: A Triple-masked Randomized Controlled Trial. Mater Sociomed. 2013;25(2):76-9. PubMed
  13. Showande SJ, Adegbolagun OM, Igbinoba SI, Fakeye TO. In vivo pharmacodynamic and pharmacokinetic interactions of Hibiscus sabdariffa calyces extracts with simvastatin. J Clin Pharm Ther. 2017;42(6):695-703.
  14. Fakeye TO, Adegoke AO, Omoyeni OC, Famakinde AA. Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation. Phytother Res. 2007;21(1):96-8.
  15. Al-Anbaki M, Nogueira RC, Cavin AL, et al. Treating uncontrolled hypertension with Hibiscus sabdariffa when standard treatment is insufficient: Pilot intervention. J Altern Complement Med. 2019;25(12):1200-1205.
  16. Ahad A, Raish M, Bin Jardan YA, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effect of Hibiscus sabdariffa and Zingiber officinale on the antihypertensive activity and pharmacokinetic of losartan in hypertensive rats. Xenobiotica. 2020:1-11.
  17. Najafpour Boushehri S, Karimbeiki R, Ghasempour S, et al. The efficacy of sour tea (Hibiscus sabdariffa L.) on selected cardiovascular disease risk factors: A systematic review and meta-analysis of randomized clinical trials. Phytother Res. 2020;34(2):329
  18. Bule M, Albelbeisi AH, Nikfar S, Amini M, Abdollahi M. The antidiabetic and antilipidemic effects of Hibiscus sabdariffa: A systematic review and meta-analysis of randomized clinical trials. Food Res Int. 2020;130:108980. PubMed
  19. Alam MA, Bin Jardan YA, Alzenaidy B, et al. Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine. J Pharm Pharmacol 2021;73(9):1151-60.

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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.

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