Major interaction on record — check this product against your medications before combining. Based on 4 of 5 ingredients. Check your meds →
Dietary supplement

Ion Ice Punch Ingredients & Drug Interactions

by Performix

Ion Ice Punch label
See full label image
Powder Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Ion Ice Punch against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Ion Ice Punch is a dietary supplement by Performix with 5 active ingredients. Its ingredients are commonly taken for mental alertness and reducing fatigue, improving athletic performance, headache and migraine relief.Based on those ingredients, 1,627 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Niacin, Caffeine, Calcium. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Ion Ice Punch by Performix

Ask about any prescription or over-the-counter medication and we check it for interactions with Ion Ice Punch by Performix — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Ion Ice Punch by Performix

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

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Aug 6, 2026

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 4 of its 12 active ingredients.
  • “Performix(TM) ION Preworkout Complex” is a proprietary blend — the label gives one combined amount (7,428 mg) without saying how much of each component you get.
  • “Sustained Muscular Performance Blend and Ballistic Energy Matrix” is a proprietary blend — the label doesn't break down how much of each component you get.

Ion Ice Punch contains 12 active ingredients formulated for pre-workout energy and muscle performance. The main players are creatine HCl for muscle strength and athletic output, caffeine for mental alertness and endurance, niacin (a B vitamin) for energy metabolism, vitamin B12 for energy and nervous system function, beta-alanine (CarnoSyn) for sustained muscle work, calcium for muscle function and electrolyte balance, citrulline malate to support blood flow and reduce fatigue, betaine anhydrous for muscle performance, and two plant extracts—bitter orange (Advantra Z) and black pepper (BioPerine) for absorption and stimulant support.

Rauwolscine, another plant compound, is included for metabolic effects. The powder also contains inactive ingredients (fillers, binders, flavors, colorants, and sweeteners) that make up the bulk of the product.

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: pre-workout muscle energy and mental focus.
  • We looked for evidence on: Athletic performance, Attention, Cognitive function, Exercise performance, Muscle strength, Workout recovery.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Creatine is rated "Possibly Effective" for Athletic performance, Muscle strength.
  • Also on file: Beta-alanine is rated "Possibly Effective" for Athletic performance.

Creatine is possibly effective for muscle strength, athletic performance, and certain brain-related conditions, though it's possibly ineffective for bone health and Huntington disease. Caffeine is likely effective for mental alertness and athletic performance, and effective for a rare neonatal breathing condition.

Niacin is likely effective for pellagra (a B-vitamin deficiency disease) and possibly effective for cholesterol and metabolic issues in HIV patients. Vitamin B12 is effective for B12 deficiency itself and effective for cyanide poisoning; it's possibly effective for canker sores.

Beta-alanine is possibly effective for athletic and physical performance, though evidence for brain function, lung disease, and other uses is insufficient. Calcium is effective for low calcium and kidney-related high potassium, and likely effective for bone density.

Bitter orange, black pepper, rauwolscine, and betaine anhydrous lack sufficient evidence to rate their effectiveness for any condition—studies haven't established reliable benefits for these ingredients as added here.

The evidence, ingredient by ingredient Caffeine Niacin Vitamin B12 Calcium

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 10 of the 10 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 10 of 10.
  • General safety write-ups exist for 10 of 10.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Creatine is generally well tolerated in healthy adults but requires caution if you have kidney problems; avoid it in pregnancy and while breastfeeding. Common side effects are dehydration, diarrhea, muscle cramps, and water retention.

Caffeine is generally safe in moderate amounts but can cause anxiety, sleep trouble, jitteriness, and dependence with regular use; high doses carry serious risk. It's possibly unsafe in pregnancy and possibly safe while nursing.

Beta-alanine is generally well tolerated but commonly causes harmless skin tingling and flushing; avoid it in pregnancy and breastfeeding due to lack of safety data. Niacin at normal food levels is safe; high-dose supplements can cause flushing, liver problems, and stomach upset—amounts from food and standard prenatal vitamins are fine, but high-dose versions should be avoided without a doctor's approval.

Calcium is generally safe at recommended doses; normal amounts are fine in pregnancy and breastfeeding. Vitamin B12 is very safe with no upper limit (excess is removed in urine) and is safe and needed in pregnancy and nursing.

Bitter orange can raise heart rate and blood pressure, especially with caffeine; avoid it in pregnancy and breastfeeding. Black pepper is safe as food but less studied as a supplement; normal dietary use is fine.

Rauwolscine has very limited human safety data and can affect heart rate and blood pressure—avoid in pregnancy and breastfeeding. Betaine is generally tolerated but can cause body odor, nausea, and diarrhea; pregnancy and breastfeeding safety isn't well established.

Side effects, ingredient by ingredient Caffeine Niacin Vitamin B12 Calcium

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 10 matched ingredients can interact with medications — Calcium, Black Pepper, Niacin, Vitamin B12, Bitter Orange, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,628 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 doctor or pharmacist before taking this product if you're on any of these medication types: HIV integrase inhibitors (dolutegravir, elvitegravir), intravenous ceftriaxone, MAOIs (older antidepressants), stimulant drugs (including ephedrine), midazolam or other sedatives, barbiturates, seizure medications, quinolone antibiotics, antipsychotics like clozapine, blood pressure drugs, anticoagulants or antiplatelet drugs (blood thinners), thyroid hormone, heart rhythm drugs, diabetes medications, cholesterol drugs (statins), anti-gout drugs, or immunosuppressants. These represent the main medication types affected by caffeine, niacin, calcium, black pepper, bitter orange, and rauwolscine in this formula.

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.

Ion Ice Punch is designed for athletes and active people who want pre-workout energy and muscle support. If you take any blood pressure medication, heart drug, blood thinner, diabetes medication, antidepressant, anti-seizure drug, or HIV medicine—especially dolutegravir or elvitegravir—you need to review your specific medications before starting this product, as several ingredients can interfere with how they work.

The caffeine and stimulant extracts also mean people with heart rhythm issues, high blood pressure, or anxiety should be especially careful. Talk it over with your own doctor or pharmacist before you start, especially if you're on any regular medications.

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

Assessment coverage: 10 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 25, 2015.

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 Ion Ice Punch, straight from the product label.

Brand Performix
Barcode (UPC) 811274020416
Net contents 8.46 oz.; 239.7 Gram(s)
Market status On market
Date entered into DSLD Mar 25, 2015
DSLD ID 43426
Product type Other Combinations
Supplement form Powder
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 Ion Ice Punch by Performix, 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:
5.3 Gram(s)
Maximum serving Sizes:
10.6 Gram(s)
Servings per container
23
UPC/BARCODE
811274020416
IngredientAmount% DV
Creatine HCl0 NP, 0 NP--
Caffeine350 mg, 175 mg--
N-Acetyl L-Tyrosine0 NP, 0 NP--
Niacin60 mg, 30 mg300%, 150%
Vitamin B121000 mcg, 500 mcg16670%, 8330%
CarnoSyn0 NP, 0 NP--
Calcium57 mg, 29 mg6%, 2%
Citrulline Malate0 NP, 0 NP--
Performix(TM) ION Preworkout Complex7428 mg, 3714 mg--
Sustained Muscular Performance Blend and Ballistic Energy Matrix0 NP, 0 NP--
Advantra Z(R) Bitter Orange (Citrus aurantium) extract0 NP, 0 NP--
BioPerine(R) Black Pepper (Piper nigrum) extract0 NP, 0 NP--
Rauwolscine (Rauvolfia canescens) extract0 NP, 0 NP--
BetaPower Betaine Anhydrous0 NP, 0 NP--

Other ingredients: Silica, Natural & Artificial flavors, Hydrogenated Vegetable Oil, Calcium Silicate, Sucralose, Microcrystalline Cellulose, Sodium Citrate, Ethylcellulose, Acesulfame Potassium, Hydroxypropyl Methylcellulose, FD&C Yellow #6, FD&C Red Dye #40

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

PERFORMIX ION embodies the PERFORMIX promise. ION uses the most advanced Multi-Phase Bead nutrient delivery system, precision engineered with ballistic Terra Intelligent Beads to disperse hard hitting ingredients in stages throughout your workout. Unlike any other pre-workout, ION releases a 2nd wave during your workout with a flood of additional anti-catabolic and metabolic energy stimulants to push you through. This innovative multi-phase system is designed to get you started, keep you going and finish strong when all others fail.

ADVANCED MULTI-PHASE EXTENDED RELEASE {image of multi-phase bead nutrient delivery system} PERFORMIX TERRA BEAD MULTI-COATING MATRIX DISPERSION COATING Intelligent rate control polymer designed for extended release ingredient profile. TERRA TARGET INGREDIENTS HYDROPHYLIC COAT Intelligent carrier control pore former within the dispersion coat provides delayed release functionality.

MULTI-PHASE PRE-WORKOUT

3 PATENTED INGREDIENTS

MAXIMUM PUMP TECHNOLOGY BALLISTIC MUSCLE ENERGY ENHANCED MENTAL FOCUS

45 SERVINGS

NATURAL & ARTIFICIAL FLAVORS

Please recycle.

MADE IN THE USA

Proudly made in the USA with carefully selected ingredients of international and domestic origin.

When used in conjunction with a regular exercise program.

cGMP GOOD MANUFACTURING PRACTICE QUALITY PRODUCT

Seals/Symbols

TERRA INTELLIGENT BEADS(TM)

{Recycle}

FDA Statement of Identity

DIETARY SUPPLEMENT

Brand IP Statement(s)

Every PERFORMIX supplement is driven by our TERRA Intelligent Dosing(TM) technology, utilizing best in class bioavailability enhancers and intelligent delivery to help maximize every single molecule's potential… period. To out perform, out last and out do.

Powered by CarnoSyn(R) trademark and patents owned by Natural Alternatives International, Inc., www.carnosyn.com Advantra Z(R) is a registered trademark of Nutratech, Inc. Bioperine is a registered trademark of Sabinsa Corporation

Precautions

WARNING: DO NOT USE IF PREGNANT, NURSING, OR PLAN ON BECOMING PREGNANT.

THIS PRODUCT IS INTENDED FOR USE BY HEALTHY ADULTS OVER THE AGE OF 18 AND SHOULD BE AVOIDED BY THOSE SENSITIVE TO CAFFEINE OR OTHER INGREDIENTS THAT HAVE KNOWN STIMULANT EFFECTS. CONTAINS 175MG OF CAFFEINE PER SERVING. Do not use this product continuously for more than 8 weeks. Do not combine with alcohol. Not intended for use by those with a medical condition. Use only as directed. Do not exceed recommended daily intake.

Do not consume synephrine or caffeine from other sources including, but not limited to, coffee, tea, soda, and other dietary supplements or medications containing phenylephrine or caffeine. Consult a physician or licensed qualified health care professional prior to use if you are pregnant or nursing, or if you are taking medication including, but not limited to, MAOI inhibitors, antidepressants, aspirin, nonsteroidal anti-inflammatory drugs or products containing phenylephrine, ephedrine, pseudoephedrine, or other stimulants, or if you have a medical condition including, but not limited to, heart, liver, kidney, or thyroid disease, psychiatric or epileptic disorders, enlarged prostate or glaucoma.

Discontinue 2 weeks prior to surgery or if you experience rapid heart beat, dizziness, severe headache or shortness of breath. DO NOT USE IF SAFETY SEAL UNDER CAP IS BROKEN.

KEEP OUT OF THE REACH OF CHILDREN.

Do not take more than 2 scoops daily.

This product should not be taken in combination with other products containing caffeine or other stimulants.

Do not take within six hours of bedtime.

CONTAINS: This product was produced in a facility that may also process ingredients containing milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat and soybeans.

Formula

CONTAINS 175MG OF CAFFEINE PER SERVING.

Storage

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

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.

General

ITEM 128-FP 1.1

Suggested/Recommended/Usage/Directions

SUGGESTED USE: As a dietary supplement, adults mix 1-2 scoops with 8 oz of water 20-30 minutes prior to workout. Start with one scoop or less to asess your tolerance.

Prior to each use, shake container vigorously to ensure evenly dispersed beads. Please read the entire label before use.

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Ion Ice Punch by Performix label

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

Ion Ice Punch label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Ion Ice Punch by Performix

These are the 5 active ingredients this product is made of. Select any to open its full monograph.

Serving size5.3 Gram(s) Dosage formPowder Servings per container23 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.

Caffeine

Interacts with
655 drugs
350 mg per serving

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredn...

Caffeine monograph & interactions

Niacin

Interacts with
727 drugs
60 mg per serving Form: Nicotinic Acid

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescr...

Niacin monograph & interactions

Vitamin B12

Interacts with
20 drugs
1000 mcg per serving Form: Methylcobalamin

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...

Vitamin B12 monograph & interactions

Calcium

Interacts with
168 drugs
57 mg per serving Form: Calcium Silicate

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

Performix(TM) ION Preworkout Complex

7428 mg per serving
  • › Sustained Muscular Performance Blend and Ballistic Energy Matrix

Other (inactive) ingredients: Silica, Natural & Artificial flavors, Hydrogenated Vegetable Oil, Calcium Silicate, Sucralose, Microcrystalline Cellulose, Sodium Citrate, Ethylcellulose, Acesulfame Potassium, Hydroxypropyl Methylcellulose, FD&C Yellow #6, FD&C Red Dye #40. These complete the product’s ingredient list but are not active constituents.

Interaction report

Ion Ice Punch by Performix Drug Interactions

Want to check YOUR meds against Ion Ice Punch?

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
1,627Drugs
25 Major 1,574 Moderate 28 Minor

Ingredients driving the most interactions

Niacin 727
Caffeine 655
Calcium 168
Vitamin B12 20

Individual Drug Interactions

The ingredients in Ion Ice Punch interact with 1,627 drugs. Click any drug to see the details.

4 of the 5 ingredients in Ion Ice Punch interact with drugs. Each result below shows which ingredient is responsible. Niacin Caffeine Calcium Vitamin B12

Each ingredient & the kinds of drugs it affects

For each ingredient in Ion Ice Punch 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.

Niacin15 drug types · 727 drugs

Alcohol (Ethanol)

Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
Alcohol can exacerbate the flushing and pruritus associated with niacin. Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine. Advise patients to avoid large amounts of alcohol while taking niacin.

Likelihood Probable Evidence D
Allopurinol (Zyloprim)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia. Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Anticoagulant/Antiplatelet Drugs

Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.

Likelihood Possible Evidence D
Antidiabetes Drugs

Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose. In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21%. However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose. In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached. Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added.

Likelihood Probable Evidence B
Antihypertensive Drugs

Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
The vasodilating effects of niacin can cause hypotension. Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients.

Likelihood Possible Evidence B
Bile Acid Sequestrants

Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30%.

Likelihood Possible Evidence D
Gemfibrozil (Lopid)

Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
A case of myopathy from concomitant use of niacin and gemfibrozil has been reported. Niacin alone has also been associated with cases of myopathy. Using gemfibrozil with niacin might further increase the risk of developing myopathy.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.

Likelihood Possible Evidence D
Hmg-Coa Reductase Inhibitors ("Statins")

Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins. However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor).

Likelihood Possible Evidence D
Probenecid (Benemid)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Sulfinpyrazone (Anturane)

Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.

Likelihood Probable Evidence C
Thyroid Hormone

Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.

Likelihood Probable Evidence D
Transdermal Nicotine (Nicoderm)

Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
Niacin and nicotine can both cause flushing and dizziness.

Likelihood Possible Evidence D
Warfarin (Coumadin)

There is limited evidence that niacin may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 3.9 after taking niacin for two weeks. The patient's INR was previously stable, ranging between 2 and 3 in recent months, and no other medication changes were identified. The elevated INR returned to therapeutic range within 4 days following the discontinuation of niacin.

Likelihood Possible Evidence D
Aspirin

Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.

Likelihood Likely Evidence B
Niacin full monograph & interactions

Caffeine41 drug types · 655 drugs

Ephedrine

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

Likelihood Probable Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

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

Likelihood Possible Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

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

Likelihood Possible Evidence D
Felbamate (Felbatol)

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

Likelihood Possible Evidence D
Flutamide (Eulexin)

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

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Pioglitazone (Actos)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Caffeine full monograph & all 41 interactions

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
Calcium full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Ion Ice Punch, from the product label.

Performix

See all Performix products
Name
Performix LLC
Street Address
221 S. Cherokee St.
City
Denver
State
CO
ZipCode
80223
Web Address
www.performixdriven.com
Pharmacist Counseling Corner

Ion Ice Punch by Performix: Common Questions

Does Ion Ice Punch by Performix interact with any medications?
Yes. Based on its ingredients, Ion Ice Punch has a known interaction with 1,627 medications, including 25 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Ion Ice Punch contains 5 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.
Will this give me that tingly feeling?
Yes, very likely. Beta-alanine (CarnoSyn) in this product commonly causes a harmless tingling and flushing sensation that usually starts on the scalp within 20 minutes and spreads to the body, lasting about an hour. This is normal and not dangerous—it's just how the ingredient feels in your system.
Can I take this if I'm pregnant or nursing?
You should talk with your doctor or pharmacist first. Creatine and beta-alanine don't have enough safety data in pregnancy and are best avoided. Caffeine is possibly unsafe in pregnancy at high doses—your provider can advise on safe limits. Niacin, calcium, and vitamin B12 at normal levels are fine. Several other ingredients lack safety information for pregnancy or nursing.
Does creatine cause water retention or kidney damage?
Creatine commonly causes water retention and mild dehydration, especially early on—that's why you see the weight-gain myths. Serious kidney problems like interstitial nephritis or renal damage are very rare and mostly reported in individual cases. If you have existing kidney disease, check with your doctor before using it, as caution is advised.
What's the black pepper extract for?
Black pepper (BioPerine) contains piperine, which is added to pre-workout formulas to help your body absorb and use the other ingredients more effectively. It's generally safe in this context, though it can increase blood levels of certain medications you might be taking.
Is this safe to mix with my other supplements?
That depends entirely on what else you're taking. Since this product contains caffeine, stimulant extracts, and niacin, combining it with other caffeine sources, energy supplements, or stimulants could amplify jitteriness and stress on your heart. Check with your pharmacist before combining any supplements or energy products.
Will this work better than plain creatine?
The evidence shows creatine itself is possibly effective for muscle strength and athletic performance—that's solid. The other ingredients here lack established proof of benefit, so you're mainly paying for a comprehensive pre-workout blend with caffeine, B vitamins, and some plant extracts. Whether it works better than plain creatine depends on whether the added ingredients suit your workout goals and tolerance.

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.

Ion Ice Punch label
Go deeper

The Full Monographs Behind Ion Ice Punch’s Ingredients

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

Herb & supplement monograph

Caffeine

Interacts with 655 drugs

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too muc...

Read the full Caffeine monograph → Herb & supplement monograph

Niacin

Interacts with 727 drugs

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescription-strength niacin has been used to...

Read the full Niacin monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 monograph → Herb & supplement monograph

Calcium

Interacts with 168 drugs

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet falls short. Most people do best getting...

Read the full Calcium monograph →
Sources

Sources & How We Checked

Ion Ice Punch'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 608 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.

Creatine 86 references
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  2. 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.
  3. Greenhaff P. Renal dysfunction accompanying oral creatine supplements. Lancet 1998;352:233-4. PubMed
  4. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training (abstract). J Appl Physiol 1997;83:2055-63. PubMed
  5. Hultman E, Soderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996;81:232-7. PubMed
  6. Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998;351:1252-3. PubMed
  7. Poortmans JR, Auquier H, Renaut V, et al. Effect of short-term creatine supplementation on renal responses in men (abstract). Eur J Appl Physiol Occup Physiol 1997;76:566-7. PubMed
  8. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999;31:1108-10. PubMed
  9. Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc 2000;32:291-6. PubMed
  10. Rawson ES, Wehnert ML, Clarkson PM. Effects of 30 days of creatine ingestion in older men. Eur J Appl Physiol Occup Physiol 1999;80:139-44. PubMed
  11. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Colch) 1996;91:113-8. PubMed
  12. Juhn MS. Oral creatine supplementation. Separating fact from hype. Phys Sportsmed 1999;27:47-50,53-54,56,61,89. PubMed
  13. Juhn MS, O'Kane JW, Vinci DM. Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am Diet Assoc 1999;99:593-5.
  14. Green AL, Hultman E, Macdonald IA, et al. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol 1996;271:E821-6. PubMed
  15. Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 1995;154:303-10. PubMed
  16. Snow RJ, McKenna MJ, Selig SE, et al. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. (abstract) J Appl Physiol 1998;84:1667-73. PubMed
  17. McNaughton LR, Dalton B, Tarr J. The effects of creatine supplementation on high-intensity exercise performance in elite performers. (abstract) Eur J Appl Physiol Occup Physiol 1998;78:236-40. PubMed
  18. Groeneveld GJ, Veldink JH, van der Tweel I, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 2003;53:437-45. . PubMed
  19. Robinson SJ. Acute quadriceps compartment syndrome and rhabdomyolysis in a weight lifter using high-dose creatine supplementation. J Am Board Fam Pract 2000;13:134-7. PubMed
  20. Kammer RT. Lone atrial fibrillation associated with creatine monohydrate supplementation. Pharmacotherapy 2005;25:762-4. PubMed
  21. Gualano B, Ugrinowitsch C, Novaes RB, et al. Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol 2008;103:33-40. PubMed
  22. Pfeffer, G., Majamaa, K., Turnbull, D. M., Thorburn, D., and Chinnery, P. F. Treatment for mitochondrial disorders. Cochrane Database.Syst.Rev. 2012;4:CD004426. PubMed
  23. 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
  24. Kreider, R. B. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med 1999;27(2):97-110. PubMed
  25. Juhn, M. S., O'Kane, J. W., and Vinci, D. M. Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am.Diet.Assoc 1999;99(5):593-595.
  26. Volek, J. S., Duncan, N. D., Mazzetti, S. A., Putukian, M., Gomez, A. L., and Kraemer, W. J. No effect of heavy resistance training and creatine supplementation on blood lipids. Int J Sport Nutr.Exerc.Metab 2000;10(2):144-156. PubMed
  27. Robinson, T. M., Sewell, D. A., Casey, A., Steenge, G., and Greenhaff, P. L. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br.J Sports Med 2000;34(4):284-288. PubMed
  28. Tarnopolsky, M. A. Potential benefits of creatine monohydrate supplementation in the elderly. Curr.Opin.Clin Nutr.Metab Care 2000;3(6):497-502. PubMed
  29. Tarnopolsky, M. A. and MacLennan, D. P. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. Int J Sport Nutr.Exerc.Metab 2000;10(4):452-463. PubMed
  30. Arciero, P. J., Hannibal, N. S., III, Nindl, B. C., Gentile, C. L., Hamed, J., and Vukovich, M. D. Comparison of creatine ingestion and resistance training on energy expenditure and limb blood flow. Metabolism 2001;50(12):1429-1434. PubMed
  31. Chrusch, M. J., Chilibeck, P. D., Chad, K. E., Davison, K. S., and Burke, D. G. Creatine supplementation combined with resistance training in older men. Med Sci.Sports Exerc. 2001;33(12):2111-2117. PubMed
  32. Cox, G., Mujika, I., Tumilty, D., and Burke, L. Acute creatine supplementation and performance during a field test simulating match play in elite female soccer players. Int J Sport Nutr.Exerc.Metab 2002;12(1):33-46. PubMed
  33. Kilduff, L. P., Vidakovic, P., Cooney, G., Twycross-Lewis, R., Amuna, P., Parker, M., Paul, L., and Pitsiladis, Y. P. Effects of creatine on isometric bench-press performance in resistance-trained humans. Med Sci.Sports Exerc. 2002;34(7):1176-1183. PubMed
  34. Brose, A., Parise, G., and Tarnopolsky, M. A. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol.Sci.Med Sci. 2003;58(1):11-19. PubMed
  35. Volek, J. S., Ratamess, N. A., Rubin, M. R., Gomez, A. L., French, D. N., McGuigan, M. M., Scheett, T. P., Sharman, M. J., Hakkinen, K., and Kraemer, W. J. The effects of creatine supplementation on muscular performance and body composition responses to
  36. Tyler, T. F., Nicholas, S. J., Hershman, E. B., Glace, B. W., Mullaney, M. J., and McHugh, M. P. The effect of creatine supplementation on strength recovery after anterior cruciate ligament (ACL) reconstruction: a randomized, placebo-controlled, double-b DOI
  37. Groeneveld, G. J., Beijer, C., Veldink, J. H., Kalmijn, S., Wokke, J. H., and van den Berg, L. H. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int J Sports Med 2005;26(4):307-313. PubMed
  38. Astorino, T. A., Marrocco, A. C., Gross, S. M., Johnson, D. L., Brazil, C. M., Icenhower, M. E., and Kneessi, R. J. Is running performance enhanced with creatine serum ingestion? J Strength.Cond.Res 2005;19(4):730-734. PubMed
  39. Cramer, J. T., Stout, J. R., Culbertson, J. Y., and Egan, A. D. Effects of creatine supplementation and three days of resistance training on muscle strength, power output, and neuromuscular function. J Strength.Cond.Res 2007;21(3):668-677. PubMed
  40. Young, P., De, Jonghe P., Stogbauer, F., and Butterfass-Bahloul, T. Treatment for Charcot-Marie-Tooth disease. Cochrane.Database.Syst.Rev. 2008;(1):CD006052. PubMed
  41. Ostojic, S. M. and Ahmetovic, Z. Gastrointestinal distress after creatine supplementation in athletes: are side effects dose dependent? Res.Sports Med. 2008;16(1):15-22. PubMed
  42. Whitt, K. N., Ward, S. C., Deniz, K., Liu, L., Odin, J. A., and Qin, L. Cholestatic liver injury associated with whey protein and creatine supplements. Semin.Liver Dis. 2008;28(2):226-231. PubMed
  43. Koenig CA, Benardot D Cody M Thompson WR. Comparison of creatine monohydrate and carbohydrate supplementation on repeated jump height performance. J Strength Cond Res. 2008;22(4):1081-1086. PubMed
  44. Gordon, P. H., Cheung, Y. K., Levin, B., Andrews, H., Doorish, C., Macarthur, R. B., Montes, J., Bednarz, K., Florence, J., Rowin, J., Boylan, K., Mozaffar, T., Tandan, R., Mitsumoto, H., Kelvin, E. A., Chapin, J., Bedlack, R., Rivner, M., McCluskey, L.
  45. Bender, A., Samtleben, W., Elstner, M., and Klopstock, T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr.Res. 2008;28(3):172-178. PubMed
  46. Parness, J. You're "hot" from pumping iron? Anesth.Analg. 2009;108(3):711-713. PubMed
  47. Gualano, B., Ferreira, D. C., Sapienza, M. T., Seguro, A. C., and Lancha, A. H., Jr. Effect of short-term high-dose creatine supplementation on measured GFR in a young man with a single kidney. Am.J.Kidney Dis. 2010;55(3):e7-e9. PubMed
  48. Saidi, H. and Mani, M. Severe metabolic acidosis secondary to coadministration of creatine and metformin, a case report. Am.J.Emerg.Med. 2010;28(3):388-6. PubMed
  49. Gualano, B., de, Salles Painelli, V, Roschel, H., Lugaresi, R., Dorea, E., Artioli, G. G., Lima, F. R., da Silva, M. E., Cunha, M. R., Seguro, A. C., Shimizu, M. H., Otaduy, M. C., Sapienza, M. T., da Costa, Leite C., Bonfa, E., and Lancha Junior, A. H.
  50. Neves, M., Jr., Gualano, B., Roschel, H., Lima, F. R., Lucia, de Sa-Pinto, Seguro, A. C., Shimizu, M. H., Sapienza, M. T., Fuller, R., Lancha, A. H., Jr., and Bonfa, E. Effect of creatine supplementation on measured glomerular filtration rate in postmeno
  51. Gufford, B. T., Sriraghavan, K., Miller, N. J., Miller, D. W., Gu, X., Vennerstrom, J. L., and Robinson, D. H. Physicochemical characterization of creatine N-methylguanidinium salts. J.Diet.Suppl 2010;7(3):240-252.
  52. Lugaresi, R., Leme, M., de, Salles Painelli, V, Murai, I. H., Roschel, H., Sapienza, M. T., Lancha Junior, A. H., and Gualano, B. Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein di
  53. Poortmans, J. R. and Francaux, M. Renal dysfunction accompanying oral creatine supplements. Lancet 7-18-1998;352(9123):234. PubMed
  54. Maganaris, C. N. and Maughan, R. J. Creatine supplementation enhances maximum voluntary isometric force and endurance capacity in resistance trained men. Acta Physiol Scand. 1998;163(3):279-287. PubMed
  55. Vandebuerie, F., Vanden Eynde, B., Vandenberghe, K., and Hespel, P. Effect of creatine loading on endurance capacity and sprint power in cyclists. Int J Sports Med 1998;19(7):490-495. PubMed
  56. Juhn, M. S. and Tarnopolsky, M. Oral creatine supplementation and athletic performance: a critical review. Clin J Sport Med 1998;8(4):286-297. PubMed
  57. Vandenberghe K, Van Hecke P, Van Leemputte M, and et al. Inhibition of muscle phosphocreatine resynthesis by caffeine after creatine loading. Med Sci Sports Exerc 1997;29(5 Supplement):249.
  58. Ziegenfuss T, Lowery LM, and Lemon PW. Acute fluid volume changes in men during three days of creatine supplementation. J Exerc Physiol Online 1998;1(3): .
  59. Kuehl K, Goldberg L, and Elliot D. Renal insufficiency after creatine supplementation in a college football athlete. Med Sci Sports Exerc 1998;30(5 Suppl ):S235. DOI
  60. Balsom PD, Ekblom B, Soderlund K, and et al. Creatine supplementation and dynamic high-intensity intermittent excercise. Scand J Med Sci Sports 1993;3:143-149.
  61. Kirksey KB, Warren BJ, Stone MH, and et al. The effects of six weeks of creatine monohydrate supplementation in male and female track athletes. Med Sci Sports Exerc 1997;29(5 Suppl):S145.
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See these in context on the Creatine monograph →

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Black Pepper 29 references
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Rauwolscine 28 references
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Betaine Anhydrous 11 references
  1. Cystadane (betaine anhydrous for oral solution) Package insert. Orphan Medical, Inc. Minnetonka, MN. November 2005.
  2. Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 2001;96:2711-7.. PubMed
  3. Schwab U, Torronen A, Toppinen L, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr 2002;76:961-7. PubMed
  4. McGregor DO, Dellow WJ, Robson RA, et al. Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure. Kidney Int 2002;61:1040-6. PubMed
  5. Olthof MR, van Vliet T, Verhoef P, et al. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PloS Med 2005;2:e135. PubMed
  6. Knopman, D. and Patterson, M. An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients. Alzheimer Dis.Assoc.Disord. 2001;15(3):162-165. PubMed
  7. Moat, S. J., Madhavan, A., Taylor, S. Y., Payne, N., Allen, R. H., Stabler, S. P., Goodfellow, J., McDowell, I. F., Lewis, M. J., and Lang, D. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest 2 PubMed
  8. Abdelmalek, M. F., Sanderson, S. O., Angulo, P., Soldevila-Pico, C., Liu, C., Peter, J., Keach, J., Cave, M., Chen, T., McClain, C. J., and Lindor, K. D. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepa PubMed
  9. Ashtary-Larky D, Bagheri R, Ghanavati M, et al. Effects of betaine supplementation on cardiovascular markers: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2021 Mar 25:1-18. PubMed
  10. Zawieja EE, Zawieja B, Chmurzynska A. Betaine supplementation moderately increases total cholesterol levels: a systematic review and meta-analysis. J Diet Suppl. 2021;18(1):105-117. PubMed
  11. Imbard A, Toumazi A, Magréault S, et al. Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial. Orphanet J Rare Dis 2022;17(1):417. PubMed

See these in context on the Betaine Anhydrous 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.

© 2021 Therapeutic Research Center, LLC

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