Major interaction on record — check this product against your medications before combining. Based on 5 of 7 ingredients. Check your meds →
Dietary supplement

Powerful Ingredients & Drug Interactions

by Xenadrine

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

Powerful is a dietary supplement by Xenadrine with 7 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis prevention, dietary calcium deficiency, heartburn relief (calcium carbonate antacids).Based on those ingredients, 1,457 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Cormino seed extract, Vitamin C, Calcium. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Powerful by Xenadrine

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

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 2 of its 11 active ingredients.
  • “Xenadrine(R) Blend” is a proprietary blend — the label gives one combined amount (488 mg) without saying how much of each component you get.
  • “Extreme Energy and Metabolic Intensifier Complex” is a proprietary blend — the label doesn't break down how much of each component you get.
  • “Powerful Weight Loss Complex” is a proprietary blend — the label doesn't break down how much of each component you get.

Xenadrine Powerful contains 11 ingredients. The active ones are calcium, vitamin C, L-carnitine, L-theanine, Frauenmantle leaf extract, wild olive leaf extract, cumin seed extract (labeled as Cormino seed extract), horsemint leaf extract, caffeine anhydrous, yohimbe bark extract, and white willow bark extract.

The product also includes inactive ingredients like microcrystalline cellulose, gelatin capsule, tricalcium phosphate, dicalcium phosphate, magnesium stearate, and silicon dioxide for structure and delivery.

Does it work?

Strong 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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: weight loss with extreme energy.
  • We looked for evidence on: Athletic performance, Chronic fatigue syndrome (CFS), Metabolic rate, Thermogenesis, Fat burning.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Yohimbe is rated "Insufficient Reliable Evidence To Rate" for Athletic performance, Fatigue.
  • Also on file: Vitamin C is rated "Insufficient Reliable Evidence To Rate" for Athletic performance, Chronic fatigue syndrome (CFS).

The evidence for most ingredients in this product is limited. Calcium is effective for kidney failure, indigestion, low blood calcium, high potassium, and likely effective for osteoporosis.

Vitamin C is effective for vitamin C deficiency and possibly effective for anemia, heart rhythm problems, cataracts, and exercise-related respiratory infections. L-carnitine is effective for L-carnitine deficiency and possibly effective for high cholesterol, heart failure, and chest pain.

For the other active ingredients—L-theanine, Frauenmantle leaf extract, wild olive leaf extract, cumin seed extract, horsemint leaf extract, caffeine, and yohimbe bark extract—the evidence we hold either shows insufficient data or does not establish effectiveness for weight loss or metabolic effects.

The evidence, ingredient by ingredient Calcium Vitamin C Olive Cumin Horsemint

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 8 of the 9 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 9 of 9.
  • General safety write-ups exist for 9 of 9.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Calcium is generally well tolerated at recommended doses, though high doses can cause problems. Common side effects include belching, constipation, diarrhea, flatulence, and stomach upset.

There is some concern that very high intakes over 1,500–2,000 mg daily may increase risk of prostate cancer and possibly cardiovascular disease, though this remains debated. Vitamin C at normal doses is well tolerated; side effects at high doses (above 2 grams daily) include abdominal cramps, heartburn, nausea, and kidney stones in susceptible people.

L-carnitine is generally well tolerated but may cause abdominal pain, diarrhea, nausea, and a fishy body odor; seizures are rare. L-theanine may cause headaches and drowsiness; long-term safety is not well studied.

Horsemint extract safety during pregnancy and breastfeeding is not established. Wild olive leaf extract is well tolerated as a supplement; headache and stomach discomfort are the most common effects.

Cumin at spice doses is safe; supplement safety data are limited. Caffeine at moderate doses is well tolerated but can cause anxiety, insomnia, tremor, nausea, and dependence with chronic use; high doses carry rare risk of stroke.

Yohimbe carries significant cardiovascular risk, causing anxiety, high blood pressure, fast heart rate, tremor, and headache—and its potency in supplements is unpredictable.

Side effects, ingredient by ingredient Calcium Vitamin C Olive Cumin Horsemint

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?
  • 7 of the 9 matched ingredients can interact with medications — Cumin, Yohimbe, Calcium, Caffeine, Vitamin C, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,458 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.

Check with your pharmacist before using Xenadrine Powerful if you take dolutegravir or elvitegravir (HIV medications), intravenous ceftriaxone (antibiotic), ephedrine (a stimulant), MAOIs or tricyclic antidepressants, warfarin or other blood thinners, oral contraceptives or hormone replacement, chemotherapy drugs, antihypertensive or blood pressure medications, thyroid hormone replacement, diabetes medications, or medications metabolized by liver enzymes CYP2D6 or CYP3A4. These represent the main interaction risks across the product's ingredients.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This product is a multi-ingredient supplement with several components that interact with common medications, especially blood thinners, heart drugs, thyroid medication, diabetes drugs, and psychiatric medications. If you take any prescriptions—particularly for blood pressure, anticoagulation, thyroid function, or mental health—check your medications with the tool on this page before starting.

Pregnant or breastfeeding individuals should talk with their pharmacist first, especially about caffeine and yohimbe. Yohimbe in particular carries cardiovascular risk and should not be used without medical guidance.

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

Assessment coverage: 9 of 11 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jun 25, 2014.

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 Powerful, straight from the product label.

Brand Xenadrine
Net contents 60 Rapid Release Capsule(s)
Market status On market
Date entered into DSLD Jun 25, 2014
DSLD ID 34301
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
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 Powerful by Xenadrine, 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 Rapid-Release Capsule(s)
Maximum serving Sizes:
2 Rapid-Release Capsule(s)
Servings per container
30
IngredientAmount% DV
Calcium70 mg7%
Vitamin C7 mg12%
L-Carnitine0 NP--
L-Theanine0 NP--
Frauenmantle leaf extract0 NP--
wild Olive leaf extract0 NP--
Cormino seed extract0 NP--
Horsemint leaf extract0 NP--
Xenadrine(R) Blend488 mg--
Extreme Energy and Metabolic Intensifier Complex0 NP--
Caffeine anhydrous0 NP--
Yohimbe bark extract0 NP--
White willow bark extract0 NP--
Powerful Weight Loss Complex0 NP--

Other ingredients: Microcrystalline Cellulose, Gelatin Capsule, Tricalcium Phosphate, Dicalcium Phosphate, Magnesium Stearate, Silicon Dioxide

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.
General Statements

POWERFUL WEIGHT LOSS Clinically Proven Key Ingredients Lose More Weight Extreme Energy Metabolic Intensifier

Made in the U.S.A. from domestic and international ingredients.

Capsule shown not actual size. For lot no. and expiry date: see box.

New Potent weight loss formula!

Made in the U.S.A. from domestic and international ingredients.

To see inspirational Xenadrine transformations, capture this QR code with a QR code application on your smartphone.

Weight loss that works! Energy you can feel!

You'll lose weight and show off a sexy body!

Metabolic intensifier A potent key ingredient (caffeine anhydrous [1,3,7-trimethylxanthine]) has been scientifically shown to support increased metabolism.

Fast weight loss in 2 clinical studies Study 1 eight weeks In study one, an 8-week randomized, double-blind, placebo-controlled clinical study funded by the makers of Xenadrine, test subjects using the key ingredients (Powerful Weight Loss Complex: frauenmantle, wild olive, cormino horsemint) lost an average of nearly 17 lbs. for the placebo group. Both groups followed a calorie-reduced diet. Study 2 twelve weeks In study two, a 12-week third-party, randomized double-blind, placebo-controlled clinically study, test subjects using the same key ingredients in Xenadrine lost an average of nearly 2 lbs. Both groups followed a calorie-reduced diet.

FDA Statement of Identity

DIETARY SUPPLEMENT

Brand IP Statement(s)

(C) 2012. Patents pending.

Xenadrine: The brand that works! Built on research and results, Xenadrine has been a reliable brand for people looking to amplify their energy and lose weight. That tradition continues with this powerful Xenadrine weight loss stimulant formula, featuring clinically proven key ingredients! Fast weight loss Designed with a key weight loss ingredient complex proven to promote powerful weight loss in 8- and 12- week clinical studies, Xenadrine can help you get the body you've always wanted, when combined with diet and exercise.

Energy for hours 3 Xenadrine has long been brand synonymous with energy, and this formula really delivers!

Precautions

WARNING: Not intended for use by persons under 18.

Do not use if you are pregnant or nursing.

Discontinue use and consult a medical doctor if you experience unusual symptoms.

Do not use if you are allergic or contraindicated to aspirin.

KEEP OUT OF REACH OF CHILDREN

Discontinue use two weeks prior to surgery or if upset stomach occurs.

Consult a medical doctor before use if you have been treated for, or diagnosed with or have a family history of any medical condition or if you are using any prescription or over-the-counter drug(s), including blood thinners.

One serving (2 capsules) of this product contains up to as much caffeine as 2 cups of coffee. Caffeine sensitive individuals may experience the following symptoms including (but not limited to) restlessness, nervousness, tremors, headache, anxiety, palpitations, increased heart rate, or difficulty sleeping. Do not combine with other sources of caffeine. Consult a medical doctor before starting a diet or exercise program. Do not exceed recommended serving. Improper use of this product will not improve results and is not advised. Use only as directed. Do not use if packaging has been tampered with.

Do not exceed recommended dosage!

Storage

Store in a cool, dry place (60(0)F to 80(0)F).

Formula

Xenadrine contains a potent key ingredient (caffeine anhydrous [1,3,7-trimethylxanthine]) that you'll feel from the very first serving, to power your busy life!

Suggested/Recommended/Usage/Directions

How to take Xenadrine Day 1 to day 3 1 rapid-release capsule with a glass of water, 30 minutes before your 3 meals of the day. Day 4 and beyond 2 rapid-release capsules with a glass of water, 30 minutes before your 3 meals of the day. ~ Use while following a calorie-reduced diet and regular exercise program. ~ Don't snack after dinner or in between meals, and remember to drink 8 to 10 glasses of water each day. ~ For best results, use Xenadrine for 8 to 12 weeks. ~ Do not exceed 6 capsules in a 24-hour period. ~ Do not take within 5 hours of bedtime. ~ Ensure you read the entire label before use and follow these directions.

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.

See for yourself

Powerful by Xenadrine label

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

What’s inside

The Ingredients in Powerful by Xenadrine

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

Serving size1 Rapid-Release Capsule(s) Dosage formCapsule Servings per container30 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.

Calcium

Interacts with
168 drugs
70 mg per serving

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet f...

Calcium monograph & interactions

Vitamin C

Interacts with
207 drugs
7 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

Xenadrine(R) Blend

488 mg per serving
  • › Extreme Energy and Metabolic Intensifier Complex

Powerful Weight Loss Complex

0 NP per serving

Other (inactive) ingredients: Microcrystalline Cellulose, Gelatin Capsule, Tricalcium Phosphate, Dicalcium Phosphate, Magnesium Stearate, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Powerful by Xenadrine Drug Interactions

Want to check YOUR meds against Powerful?

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
1,457Drugs
24 Major 1,040 Moderate 393 Minor

Ingredients driving the most interactions

Vitamin C 207
Calcium 168

Each ingredient & the kinds of drugs it affects

For each ingredient in Powerful 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.

Cormino seed extract3 drug types · 211 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, cumin might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
In vitro evidence suggests that cumin can inhibit platelet aggregation. Theoretically, cumin might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, cumin might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research suggests that cumin can lower blood sugar in diabetic animals. However, research in humans with and without diabetes has found conflicting results.

Likelihood Probable Evidence D
Rifampin (Rifadin)

Theoretically, cumin might increase the effects and adverse effects of rifampin.
Animal research suggests that an aqueous extract of cumin containing a specific flavonoid glycoside can increase the bioavailability and plasma levels of rifampin.

Likelihood Possible Evidence D

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

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Likelihood Probable Evidence B
Aluminum

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Likelihood Possible Evidence B
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

Taking calcipotriene with calcium might increase the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Likelihood Probable Evidence B
Lithium

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Likelihood Possible Evidence B
Quinolone Antibiotics

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Likelihood Probable Evidence B
Raltegravir (Isentress)

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Likelihood Possible Evidence B
Sotalol (Betapace)

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Likelihood Possible Evidence B
Tetracycline Antibiotics

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Likelihood Probable Evidence C
Thiazide Diuretics

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Likelihood Probable Evidence C
Verapamil (Calan, Others)

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Likelihood Probable Evidence D
Calcium Channel Blockers

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Likelihood Unlikely Evidence D
The maker

Brand information

Manufacturer and brand details for Powerful, from the product label.

Xenadrine

See all Xenadrine products
Name
Iovate Health Sciences U.S.A. Inc.
Street Address
1105 Market Street, Suite 1330
City
Wilmington
State
DE
ZipCode
19801
Pharmacist Counseling Corner

Powerful by Xenadrine: Common Questions

Does Powerful by Xenadrine interact with any medications?
Yes. Based on its ingredients, Powerful has a known interaction with 1,457 medications, including 24 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Powerful 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.
Can I take this if I'm on warfarin or another blood thinner?
No, not without your doctor's approval. Multiple ingredients—vitamin C at high doses, L-carnitine, and cumin seed extract—may increase bleeding risk or reduce warfarin effectiveness. Talk to your pharmacist or doctor before starting this product.
What's the caffeine content, and will it keep me awake?
The product contains caffeine anhydrous, though the exact amount per dose isn't specified in the facts we hold. Yes, caffeine commonly causes insomnia, anxiety, and restlessness—especially at higher doses. If you're sensitive to caffeine or take it late in the day, sleep disruption is likely.
Is it safe to take while pregnant or breastfeeding?
There isn't enough safety data for most ingredients in this product during pregnancy or breastfeeding. Yohimbe is considered unsafe in pregnancy. Caffeine in high amounts may carry pregnancy risks. Talk to your doctor or pharmacist before using it if you're pregnant or nursing.
Does this product actually help with weight loss?
The facts we hold don't show established effectiveness for weight loss or metabolism from the ingredients in Xenadrine Powerful. Effectiveness ratings for most of these components are either insufficient or not related to weight loss.
What are the most common side effects?
Common side effects depend on the ingredient but include stomach upset, nausea, diarrhea, and constipation from calcium and L-carnitine; headache and nausea from vitamin C at high doses; anxiety, insomnia, and jitteriness from caffeine; and anxiety, high blood pressure, and tremor from yohimbe. Individual tolerance varies widely.
Can I take this with my antidepressant?
It depends on which antidepressant. Yohimbe bark extract can cause serious problems with tricyclic antidepressants and should not be combined with MAOIs. Talk to your pharmacist about your specific medication before starting.

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.

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The Full Monographs Behind Powerful’s Ingredients

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

Sources

Sources & How We Checked

Powerful'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 475 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.

Calcium 62 references
  1. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
  3. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183-9. PubMed
  4. Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
  5. Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
  6. Saunders D, Sillery J, Chapman R. Effect of calcium carbonate and aluminum hydroxide on human intestinal function. Dig Dis Sci 1988;33:409-13. PubMed
  7. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
  9. Raman L, Rajalakshmi K, Krishnamachari KAVR, et al. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the neonates. Am J Clin Nutr 1978; 31:466-9. DOI
  10. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  11. Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 1998;9:559-66.
  12. Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
  13. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
  14. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. PubMed
  15. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
  16. Kahela P, Anttila M, Tikkanen R, Sundquist H. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol (Copenh) 1979;44:7-12.. PubMed
  17. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  18. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  19. Decktor DL, Robinson M, Maton PN, et al. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995;2:546-52. PubMed
  20. Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
  21. Peters ML, Leonard M, Licata AA. Role of alendronate and risedronate in preventing and treating osteoporosis. Cleve Clin J Med 2001;68:945-51. PubMed
  22. Bourke JF, Mumford R, Whittaker P, et al. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 1997;37:929-34.
  23. Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
  24. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
  25. Bania TC, Blaufeux B, Hughes S, et al. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med 2000;7:1089-96. PubMed
  26. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 2005;81:1147-54. PubMed
  27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
  28. Tavani A, Bertuccio P, Bosetti C, et al. Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 2005;48:27-33. PubMed
  29. Giovannucci E, Liu Y, Stampfer MJ, Willett WC. A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:203-10. PubMed
  30. Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
  31. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised control trial. BMJ 2008;336:262-6.
  32. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. PubMed
  33. Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
  34. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  35. Coburn JW, Mischel MG, Goodman WG, et al. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-11. PubMed
  36. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-13. PubMed
  37. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  38. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. DOI
  39. Dickinson, H. O., Nicolson, D. J., Cook, J. V., Campbell, F., Beyer, F. R., Ford, G. A., and Mason, J. Calcium supplementation for the management of primary hypertension in adults. Cochrane.Database.Syst.Rev. 2006;(2):CD004639. PubMed
  40. Jones, B. J. and Twomey, P. J. Requesting patterns for serum calcium concentration in patients on long-term lithium therapy. Int J Clin Pract. 2009;63(1):170-172. PubMed
  41. Levine, M., Nikkanen, H., and Pallin, D. J. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg.Med. 2011;40(1):41-46. PubMed
  42. Castelo-Branco, C., Ciria-Recasens, M., Cancelo-Hidalgo, M. J., Palacios, S., Haya-Palazuelos, J., Carbonell-Abello, J., Blanch-Rubio, J., Martinez-Zapata, M. J., Manasanch, J., and Perez-Edo, L. Efficacy of ossein-hydroxyapatite complex compared with ca
  43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation i
  44. Chung M, Tang AM, Fu Z. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 25. PubMed
  45. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38(5):937-41. PubMed
  46. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res PubMed
  47. 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
  48. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  49. Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
  50. Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
  51. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacotherapy 2011;31(10):298e-302e. DOI
  52. Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
  53. Storan ER, O'Gorman SM, Murphy A, Laing M. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D<sub>3</sub> Supplementation. J Cutan Med Surg. 2017;21(2):162-163. DOI
  54. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  55. Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
  56. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ anc-positive-pregnancy-experience/en/).
  57. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117. PubMed
  58. Lan T, Park Y, Colditz GA, et al. Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study. Cancer Causes Control. 2020;31(10):891-904. PubMed
  59. Zhang Y, Li Y, Liu J, et al. Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis. J Nutr Health Aging 2021;25(2):263-270. PubMed
  60. Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients 2021;13(2):368. PubMed
  61. Hetaimish B. Neonatal Calcinosis Cutis After Treatment of Hypocalcemia with Calcium Gluconate: A Report of 2 Cases. Am J Case Rep 2024;25:e943397. PubMed
  62. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Calcium monograph →

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 →

L-carnitine 41 references
  1. Ellaway CM, Williams K, Leonard H, et al. Rett syndrome: randomized controlled trial of L-carnitine. J Child Neurol 1999;14:162-7. PubMed
  2. Anon. Carnitor (levocarnitine) package insert. Sigma-Tau Pharmaceuticals Inc, Gaithersburg, MD. December 1999.
  3. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo-controlled, crossover study. Int J Clin Pharmacol Ther Toxicol 1985;23:569-72.
  4. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology 1997;35:16-23. PubMed
  5. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Meta
  6. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
  7. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385. PubMed
  8. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;42:941-67. PubMed
  9. 12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67. PubMed
  10. Ciacci C, Peluso G, Iannoni E, et al. L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study. Dig Liver Dis 2007;39:922-8. PubMed
  11. Cruciani RA, Dvorkin E, Homel P, et al. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage 2006;32:551-9. PubMed
  12. Lebrun C, Alchaar H, Candito M, et al. Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue. Mult Scler 2006;12:321-4. PubMed
  13. Malaguarnera M, Cammalleri L, Gargante MP, et al. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86:1738-44. PubMed
  14. Mantovani G, Maccio A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 322 patients with cancer cachexia. Oncologist 2010;15:200-11.
  15. Angelova-Fischer I, Rippke F, Fischer TW, Neufang G, Zillikens D. A double-blind, randomized, vehicle-controlled efficacy assessment study of a skin care formulation for improvement of mild to moderately severe acne. J Eur Acad Dermatol Venereol. 2013 Jul PubMed
  16. Hatamkhani S, Khalili H, Karimzadeh I, Dashti-Khavidaki S, Abdollahi A, Jafari S. Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a randomized, clinical trial. J Gastroenterol. Hepatol. 2014 May;29(5):997-1004. PubMed
  17. Boehm G, Stahl B. Oligosaccharides from milk. J Nutr 2007;137(3 Suppl 2):847S-849S.
  18. Van Oudheusden, L. J. and Scholte, H. R. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot.Essent.Fatty Acids 2002;67(1):33-38. PubMed
  19. Derosa, G., Cicero, A. F., Gaddi, A., Mugellini, A., Ciccarelli, L., and Fogari, R. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 2003;25(5):1429-1439. PubMed
  20. Foitzik, K., Hoting, E., Heinrich, U., Tronnier, H., and Paus, R. Indications that topical L-carnitin-L-tartrate promotes human hair growth in vivo. J Dermatol.Sci 2007;48(2):141-144. PubMed
  21. Kumar, A., Singh, R. B., Saxena, M., Niaz, M. A., Josh, S. R., Chattopadhyay, P., Mechirova, V., Pella, D., and Fedacko, J. Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study. Acta Cardiol. 20
  22. Cruciani, R. A., Dvorkin, E., Homel, P., Culliney, B., Malamud, S., Lapin, J., Portenoy, R. K., and Esteban-Cruciani, N. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pa PubMed
  23. Malaguarnera, M., Vacante, M., Avitabile, T., Malaguarnera, M., Cammalleri, L., and Motta, M. L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin.Nutr 2009;89(1):71-76. PubMed
  24. Alvarez, T. M., Guardiola, P. D., Roldan, J. O., Elviro, R., Wevers, R., and Guijarro, G. [Primary trimethylaminuria: the fish odor syndrome]. Endocrinol.Nutr. 2009;56(6):337-340.
  25. Wu, Z. M., Lu, X., Wang, Y. W., Sun, J., Tao, J. W., Yin, F. H., and Cheng, H. J. [Short-term medication of L-carnitine before intracytoplasmic sperm injection for infertile men with oligoasthenozoospermia]. Zhonghua Nan.Ke.Xue 2012;18(3):253-256.
  26. Tarighat, Esfanjani A., Mahdavi, R., Ebrahimi, Mameghani M., Talebi, M., Nikniaz, Z., and Safaiyan, A. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol.Trace Elem.Res 2012;150(1-3): PubMed
  27. DiNicolantonio, J. J., Lavie, C. J., Fares, H., Menezes, A. R., and O'Keefe, J. H. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-551. PubMed
  28. Huang, W. W., Wang, M. Y., Shi, H. M., Peng, Y., Peng, C. S., Zhang, M., Li, Y., Lu, J., and Li, X. B. Comparative study of bioactive constituents in crude and processed Glycyrrhizae radix and their respective metabolic profiles in gastrointestinal tract
  29. Madsen KL, Preisler N, Orngreen MC, Andersen SP, Olesen JH, Lund AM, Vissing J. Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation. J Clin Endocri
  30. Prohaska ES, Muzyk AJ, Rivelli SK. Levocarnitine-induced hypophosphatemia in a hemodialysis patient with acute valproic acid toxicity. J Neuropsychiatry Clin Neurosci. 2012 Winter;24(1):E18-9. PubMed
  31. Shang R, Sun Z, Li H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2014 Jul 21;14:88. PubMed
  32. Zhang JJ, Wu ZB, Cai YJ, Ke B, Huang YJ, Qiu CP, Yang YB, Shi LY, Qin J. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study. Nutr J. 2014 Nov 26;13:110. PubMed
  33. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carn
  34. Jun DW, Kim BI, Cho YK, Kim HJ, Kwon YO, Park SY, Han SY, Baek YH, Jung YJ, Kim HY, Kim W, Heo J, Woo HY, Hwang SG, Rim KS, Choi JY, Bae SH, Lee YS, Lim YS,Cheong JY, Cho SW, Lee BS, Kim SH, Sohn JH, Kim TY, Paik YH, Kim JK, Lee KS. Efficacy and safety of
  35. An JH, Kim YJ, Kim KJ, et al. L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial. Endocr J. 2016;63(10):885-95. PubMed
  36. Chen N, Yang M, Zhou M, Xiao J, Guo J, He L. L-carnitine for cognitive enhancement in people without cognitive impairment. Cochrane Database Syst Rev. 2017;3:CD009374. PubMed
  37. Khajeh B, Dashti-Khavidaki S, Nasiri-Toosi M, Mohammadi K, Jafari A. Effects of pre-transplant L-carnitine supplementation on primary graft dysfunction in liver transplant recipients: a pilot, randomized, placebo-controlled clinical trial. Res Pharm Sci. PubMed
  38. Kubota K, Uojima H, Shao X, et al. Additional L-carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin. Dig Dis 2021. PubMed
  39. Amini L, Yaghini O, Ghazavi M, Aslani N. L-carnitine versus propranolol for pediatric migraine prophylaxis. Iran J Child Neurol 2021;15(2):77-86.
  40. Shakibaei F, Jelvani D. Effect of adding l -carnitine to risperidone on behavioral, cognitive, social, and physical symptoms in children and adolescents with autism: A randomized double-blinded placebo-controlled clinical trial. Clin Neuropharmacol 2023;4 PubMed
  41. Moustafa I, Connolly C, Anis M, Mustafa H, Oosthuizen F, Viljoen M. A prospective study to evaluate the efficacy and safety of vitamin E and levocarnitine prophylaxis against doxorubicin-induced cardiotoxicity in adult breast cancer patients. J Oncol Phar PubMed

See these in context on the L-carnitine 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 →

Olive 2 references
  1. Liccardi G, D'Amato M, D'Amato G. Oleaceae pollinosis: a review. Int Arch Allergy Immunol 1996;111:210-7. PubMed
  2. Somerville V, Moore R, Braakhuis A. The effect of olive leaf extract on upper respiratory illness in high school athletes: A randomised control trial. Nutrients. 2019;11(2). pii: E358. PubMed

See these in context on the Olive monograph →

Cumin 10 references
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  2. Anliker, M. D., Borelli, S., and Wuthrich, B. Occupational protein contact dermatitis from spices in a butcher: a new presentation of the mugwort-spice syndrome. Contact Dermatitis 2002;46(2):72-74. PubMed
  3. Dhandapani, S., Subramanian, V. R., Rajagopal, S., and Namasivayam, N. Hypolipidemic effect of Cuminum cyminum L. on alloxan-induced diabetic rats. Pharmacol.Res 2002;46(3):251-255. PubMed
  4. Sachin, B. S., Sharma, S. C., Sethi, S., Tasduq, S. A., Tikoo, M. K., Tikoo, A. K., Satti, N. K., Gupta, B. D., Suri, K. A., Johri, R. K., and Qazi, G. N. Herbal modulation of drug bioavailability: enhancement of rifampicin levels in plasma by herbal pro
  5. Jagtap, A. G. and Patil, P. B. Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats. Food Chem.Toxicol. 5-6-2010; PubMed
  6. Srivastava, K. C. Extracts from two frequently consumed spices--cumin (Cuminum cyminum) and turmeric (Curcuma longa)--inhibit platelet aggregation and alter eicosanoid biosynthesis in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1989;3 PubMed
  7. Futrell, J. M. and Rietschel, R. L. Spice allergy evaluated by results of patch tests. Cutis 1993;52(5):288-290.
  8. Boxer, M., Roberts, M., and Grammer, L. Cumin anaphylaxis: a case report. J.Allergy Clin.Immunol. 1997;99(5):722-723. PubMed
  9. Karimian J, Farrokhzad A, Jalili C. The effect of cumin (Cuminum cyminum L.) supplementation on glycemic indices: A systematic review and meta-analysis of randomized controlled trials. Phytother Res 2021;35(8):4127-4135.
  10. Tavakoli-Rouzbehani OM, Faghfouri AH, Anbari M, et al. The effects of Cuminum cyminum on glycemic parameters: a systematic review and meta-analysis of controlled clinical trials. J Ethnopharmacol 2021;281:114510. PubMed

See these in context on the Cumin monograph →

Horsemint 1 reference
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.

See these in context on the Horsemint 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, Brants&aelig;ter 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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Yohimbe 66 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  5. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  6. Teloken C, Rhoden EL, Sogari P, et al. Therapeutic effects of high dose yohimbine hydrochloride on organic erectile dysfunction. J Urol 1998;159:122-4. PubMed
  7. Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53:119-22.
  8. Hollander E, McCarley A. Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers. J Clin Psychiatry 1992;53:207-9.
  9. Sandler B, Aronson P. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urol 1993;41:343-5. PubMed
  10. Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a retrospective review of the California Poison Control System reported cases. Ann Pharmacother 2010;44:1022-9. PubMed
  11. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
  12. Abebe, W. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations. J Dent.Hyg. 2003;77(1):37-46.
  13. Mustonen, P., Savola, J., and Lassila, R. Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human platelets and inhibits their adrenaline-induced aggregation more effectively than yohimbine. Thromb.Res 8-1-2000;99(3):231-237.
  14. Cameron, O. G., Zubieta, J. K., Grunhaus, L., and Minoshima, S. Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans. Psychosom.Med 2000;62(4):549-559. PubMed
  15. Bowes, M. P., Peters, R. H., Kernan, W. J., Jr., and Hopper, D. L. Effects of yohimbine and idazoxan on motor behaviors in male rats. Pharmacol.Biochem.Behav. 1992;41(4):707-713.
  16. Bagheri, H., Schmitt, L., Berlan, M., and Montastruc, J. L. Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1992;34(6):555-558. PubMed
  17. Bagheri, H., Bompart, G., Girolami, J. P., Montastruc, J. L., and Montastruc, P. Is yohimbine-induced increase in salivary secretion a kinin-dependent mechanism? Fundam.Clin Pharmacol 1992;6(1):17-20. PubMed
  18. Swann, A. C., Birnbaum, D., Jagar, A. A., Dougherty, D. M., and Moeller, F. G. Acute yohimbine increases laboratory-measured impulsivity in normal subjects. Biol.Psychiatry 5-15-2005;57(10):1209-1211. PubMed
  19. Adeniyi, A. A., Brindley, G. S., Pryor, J. P., and Ralph, D. J. Yohimbine in the treatment of orgasmic dysfunction. Asian J Androl 2007;9(3):403-407. PubMed
  20. Murburg, M. M., Villacres, E. C., Ko, G. N., and Veith, R. C. Effects of yohimbine on human sympathetic nervous system function. J Clin Endocrinol.Metab 1991;73(4):861-865. PubMed
  21. Giampreti, A., Lonati, D., Locatelli, C., Rocchi, L., and Campailla, M. T. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol.(Phila) 2009;47(8):827-829. PubMed
  22. Bloomer, R. J., Canale, R. E., Blankenship, M. M., Hammond, K. G., Fisher-Wellman, K. H., and Schilling, B. K. Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized,
  23. Myers, A. and Barrueto, F., Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol. 2009;5(4):223-225.
  24. Berlin, I., Crespo-Laumonnier, B., Cournot, A., Landault, C., Aubin, F., Legrand, J. C., and Puech, A. J. The alpha 2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects. Clin Pharmacol.Ther. 199
  25. Swann, A. C. Mechanisms of impulsivity in bipolar disorder and related illness. Epidemiol.Psichiatr.Soc. 2010;19(2):120-130.
  26. Shibao, C., Okamoto, L. E., Gamboa, A., Yu, C., Diedrich, A., Raj, S. R., Robertson, D., and Biaggioni, I. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 2010;56(5) PubMed
  27. Soeter, M. and Kindt, M. Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation. Neuropsychopharmacology 2012;37(5):1204-1215. PubMed
  28. Cimolai, N. and Cimolai, T. Yohimbine use for physical enhancement and its potential toxicity. J Diet.Suppl 2011;8(4):346-354. PubMed
  29. Bagheri, H., Berlan, M., Montastruc, J. L., and Montastruc, P. Yohimbine and lacrimal secretion. Br J Clin Pharmacol. 1990;30(1):151-152.
  30. Landis, E. and Shore, E. Yohimbine-induced bronchospasm. Chest 1989;96(6):1424. PubMed
  31. Susset, J. G., Tessier, C. D., Wincze, J., Bansal, S., Malhotra, C., and Schwacha, M. G. Effect of yohimbine hydrochloride on erectile impotence: a double-blind study. J Urol. 1989;141(6):1360-1363. PubMed
  32. Chatelut, E., Rispail, Y., Berlan, M., and Montastruc, J. L. Yohimbine increases human salivary secretion. Br.J Clin Pharmacol. 1989;28(3):366-368. PubMed
  33. Montastruc, P., Berlan, M., and Montastruc, J. L. Effects of yohimbine on submaxillary salivation in dogs. Br J Pharmacol 1989;98(1):101-104. PubMed
  34. Charney, D. S., Price, L. H., and Heninger, G. R. Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action. Arch.Gen.Psychiatry 1986;43(12):1155-1161. PubMed
  35. Braddock, L., Cowen, P. J., Elliott, J. M., Fraser, S., and Stump, K. Binding of yohimbine and imipramine to platelets in depressive illness. Psychol.Med 1986;16(4):765-773. PubMed
  36. Bolme, P., Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., and Goldstein, M. Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur J Pharm PubMed
  37. Charney, D. S., Heninger, G. R., and Sternberg, D. E. Assessment of alpha 2 adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci 6-7-1982;30(23):2033-2041.
  38. Boon, N. A., Elliott, J. M., Grahame-Smith, D. G., John-Green, T., and Stump, K. A comparison of alpha 2-adrenoreceptor binding characteristics of intact human platelets identified by [3H]-yohimbine and [3H]- dihydroergocryptine. J Auton.Pharmacol 1983;3
  39. Andrejak, M., Ward, M., and Schmitt, H. Cardiovascular effects of yohimbine in anaesthetized dogs. Eur.J Pharmacol 10-28-1983;94(3-4):219-228. PubMed
  40. Brodde, O. E., Anlauf, M., Arroyo, J., Wagner, R., Weber, F., and Buck, K. D. Hypersensitivity of adrenergic receptors and blood-pressure response to oral yohimbine in orthostatic hypotension. N.Engl.J Med 4-28-1983;308(17):1033-1034. PubMed
  41. Charney, D. S., Heninger, G. R., and Redmond, D. E., Jr. Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci. 7-4-1983;33(1):19-29. PubMed
  42. Knoll, L. D., Benson, R. C., Jr., Bilhartz, D. L., Minich, P. J., and Furlow, W. L. A randomized crossover study using yohimbine and isoxsuprine versus pentoxifylline in the management of vasculogenic impotence. J Urol. 1996;155(1):144-146. DOI
  43. Betz, J. M., White, K. D., and der Marderosian, A. H. Gas chromatographic determination of yohimbine in commercial yohimbe products. J AOAC Int 1995;78(5):1189-1194. DOI
  44. Bagheri, H., Chale, J. J., Guyen, L. N., Tran, M. A., Berlan, M., and Montastruc, J. L. Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. Fundam.Clin Pharmacol 1995;9(3):248-254.
  45. Kennedy, S. H., Gnam, W., Ralevski, E., and Brown, G. M. Melatonin responses to clonidine and yohimbine challenges. J Psychiatry Neurosci. 1995;20(4):297-304.
  46. Musso, N. R., Vergassola, C., Pende, A., and Lotti, G. Yohimbine effects on blood pressure and plasma catecholamines in human hypertension. Am J Hypertens. 1995;8(6):565-571. PubMed
  47. Morgan, C. A., III, Southwick, S. M., Grillon, C., Davis, M., Krystal, J. H., and Charney, D. S. Yohimbine-facilitated acoustic startle reflex in humans. Psychopharmacology (Berl) 1993;110(3):342-346. PubMed
  48. Adler, L. E., Hoffer, L., Nagamoto, H. T., Waldo, M. C., Kisley, M. A., and Giffith, J. M. Yohimbine impairs P50 auditory sensory gating in normal subjects. Neuropsychopharmacology 1994;10(4):249-257. PubMed
  49. Biaggioni, I., Robertson, R. M., and Robertson, D. Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure. J Clin Pharmacol. 1994;34(5):418-423. PubMed
  50. Kenney, W. L., Zappe, D. H., Tankersley, C. G., and Derr, J. A. Effect of systemic yohimbine on the control of skin blood flow during local heating and dynamic exercise. Am J Physiol 1994;266(2 Pt 2):H371-H376. PubMed
  51. Friesen, K., Palatnick, W., and Tenenbein, M. Benign course after massive ingestion of yohimbine. J Emerg.Med 1993;11(3):287-288. PubMed
  52. Bierer, L. M., Aisen, P. S., Davidson, M., Ryan, T. M., Stern, R. G., Schmeidler, J., and Davis, K. L. A pilot study of oral physostigmine plus yohimbine in patients with Alzheimer disease. Alzheimer Dis.Assoc.Disord. 1993;7(2):98-104. PubMed
  53. Mann, K., Klingler, T., Noe, S., Roschke, J., Muller, S., and Benkert, O. Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction. Arch.Sex Behav. 1996;25(1):1-16. PubMed
  54. Rowland, D. L., Kallan, K., and Slob, A. K. Yohimbine, erectile capacity, and sexual response in men. Arch Sex Behav 1997;26(1):49-62.
  55. Bremner, J. D., Innis, R. B., Ng, C. K., Staib, L. H., Salomon, R. M., Bronen, R. A., Duncan, J., Southwick, S. M., Krystal, J. H., Rich, D., Zubal, G., Dey, H., Soufer, R., and Charney, D. S. Positron emission tomography measurement of cerebral metaboli
  56. Riley AJ, Goodman R, Kellett JM, and et al. Double blind trial of yohimbine hydrochloride in the treatment of erection inadequacy. Sexual Marital Ther 1989;4(1):17-26. DOI
  57. Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2015 Sep 22. PubMed
  58. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Am J Emerg Med. 1999;17:317-318. PubMed
  59. Wylie KR. Yohimbine and sinusitis. Br J Psychiatry. 1996;169(3):384-5. PubMed
  60. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  61. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  62. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  63. Schmauss M, Laakmann G, Dieterle D. Effects of alpha 2-receptor blockade in addition to tricyclic antidepressants in therapy-resistant depression. J Clin Psychopharmacol. 1988;8(2):108-11.
  64. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  65. Hodapp B, Haggerty A, Feldman R, Timpe J. Intracranial hemorrhage after a single dose of Yohimbine in a chronic user of clonidine. Am J Emerg Med 2022;62:145. PubMed
  66. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. PubMed

See these in context on the Yohimbe monograph →

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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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