Major interaction on record — check this product against your medications before combining. Based on 13 of 15 ingredients. Check your meds →
Dietary supplement

Cardio-Stolix Ingredients & Drug Interactions

by Douglas Laboratories

Cardio-Stolix label
See full label image
Capsule 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 Cardio-Stolix 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

Cardio-Stolix is a dietary supplement by Douglas Laboratories with 15 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,298 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Coleus extract, MegaNatural(R)-BP grape seed extract, L-Arginine. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Cardio-Stolix by Douglas Laboratories

Ask about any prescription or over-the-counter medication and we check it for interactions with Cardio-Stolix by Douglas Laboratories — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Cardio-Stolix by Douglas Laboratories

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 Jul 12, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 13 of its 15 active ingredients.
  • “Valyl-Prolyl-Proline and Isoleucyl-Prolyl-Proline” is listed as a grouped ingredient — the label gives one combined amount (3.40 mg) without saying how much of each component you get.

Cardio-Stolix contains 15 active ingredients: Vitamin B6, Folic Acid, Calcium, Vitamin B12, L-Arginine, Hawthorn extract, Coleus extract, Olive leaf extract, Nattokinase, Vitamin C, Magnesium, AmealPeptide(R) Hydrolyzed Casein, and Valyl-Prolyl-Proline and Isoleucyl-Prolyl-Proline (lactotripeptides). These work together to support cardiovascular function through different pathways — B vitamins aid metabolism and homocysteine regulation, minerals support heart rhythm and blood vessel function, botanical extracts like hawthorn and coleus may enhance circulation, nattokinase supports healthy blood flow, and the casein peptides have been studied for modest blood-pressure support.

The product also contains cellulose and vegetable stearate as inactive ingredients.

Does it work?

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

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

Why this rating?
  • The label markets this product for: Heart health and cardiovascular support.
  • We looked for evidence on: Angina, Arrhythmia, Atherosclerosis, Atrial fibrillation, Angioplasty, High blood pressure — and 2 related terms.
  • The strongest evidence on file: Magnesium is rated "Possibly Effective" for Vasospastic angina (Natural Medicines).
  • Also on file: Magnesium is rated "Possibly Effective" for Arrhythmia.
  • Also on file: Vitamin C is rated "Possibly Effective" for Atrial fibrillation.

The evidence for Cardio-Stolix's effectiveness is mixed and depends on the ingredient. Vitamin B6 and Folic Acid are established as effective for specific deficiencies and conditions like pregnancy-related nausea (B6, possibly effective) and neural tube defect prevention (folic acid, likely effective).

Calcium is effective for low calcium and likely effective for bone health. Vitamin B12 is effective for deficiency and B12-related conditions.

Magnesium is effective for constipation and heartburn, and likely effective for pre-eclampsia. AmealPeptide(R) Hydrolyzed Casein is likely effective for food allergies and atopic dermatitis.

However, hawthorn, coleus, nattokinase, olive leaf extract, and grape seed extract all carry ratings of insufficient reliable evidence or possibly ineffective for cardiovascular conditions like angina, heart failure, and atherosclerosis — meaning the data we hold does not establish that they work for those purposes.

The evidence, ingredient by ingredient Vitamin B6 Folic Acid Calcium Vitamin B12 L-arginine Hawthorn Coleus Olive

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 12 of the 13 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 13 of 13.
  • General safety write-ups exist for 13 of 13.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients in Cardio-Stolix are generally well tolerated at recommended doses. Vitamin B6 is safe at normal amounts but high doses over time can harm nerves (a rare but serious risk).

Vitamin B12 is considered very safe with no upper limit. Folic acid is generally safe at recommended doses and considered safe during pregnancy.

Calcium, Vitamin C, Magnesium, and Olive leaf extract are all well tolerated in standard amounts, though high-dose vitamin C can cause kidney stones and high-dose magnesium may weaken bones. L-Arginine, Hawthorn, Coleus, and Nattokinase are less studied long-term and carry cautions — hawthorn and coleus should be avoided in pregnancy due to insufficient data, and nattokinase carries bleeding risk.

Grape seed extract appears well tolerated but should be avoided during pregnancy. Several ingredients note that concentrated supplement forms are less studied than whole food versions.

Side effects, ingredient by ingredient Vitamin B6 Folic Acid Calcium Vitamin B12 L-arginine Hawthorn Coleus Olive

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?
  • 12 of the 13 matched ingredients can interact with medications — Grape, Hawthorn, Calcium, L-arginine, Vitamin B12, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,299 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Cardio-Stolix, double-check with your pharmacist if you take any blood pressure medications (antihypertensive drugs), blood thinners or antiplatelet drugs, seizure medications (phenobarbital or phenytoin), HIV integrase inhibitors (dolutegravir or elvitegravir), heart rhythm medications (amiodarone), diabetes drugs, levodopa/carbidopa for Parkinson's disease, or cancer chemotherapy drugs. These are the medication types with the most serious or most numerous interactions in this product.

No interactions are documented for the individual components Valyl-Prolyl-Proline or Isoleucyl-Prolyl-Proline, as we could not check them.

Check your own medication Run your meds through the checker above

The bottom line

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

Cardio-Stolix may be of interest to people seeking a multi-ingredient approach to cardiovascular support, particularly those with specific nutrient gaps like B12 or folate deficiency. However, if you take medications for HIV, heart rhythm, blood pressure, blood clotting, seizure control, or diabetes, you must check this product against your exact prescription list before starting — the interactions are real and some are serious.

Talk to your pharmacist or doctor to see if this product and your current medications can safely be used together.

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

Assessment coverage: 13 of 15 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 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 Cardio-Stolix, straight from the product label.

Brand Douglas Laboratories
Barcode (UPC) 310539039205
Net contents 120 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Mar 25, 2014
DSLD ID 31047
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Cardio-Stolix by Douglas Laboratories, 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:
4 Vegetarian Capsule(s)
Maximum serving Sizes:
4 Vegetarian Capsule(s)
Servings per container
30
UPC/BARCODE
310539039205
IngredientAmount% DV
Vitamin B610 mg500%
Folic Acid800 mcg200%
Calcium50 mg5%
Vitamin B12500 mcg8333%
L-Arginine150 mg--
Hawthorn extract250 mg--
Coleus extract125 mg--
Olive leaf extract75 mg--
Nattokinase500 FU--
Vitamin C250 mg417%
Magnesium100 mg25%
AmealPeptide(R) Hydrolyzed Casein508 mg--
Valyl-Prolyl-Proline and Isoleucyl-Prolyl-Proline3.4 mg--
Valyl-Prolyl-Proline0 NP--
Isoleucyl-Prolyl-Proline0 NP--
MegaNatural(R)-BP grape seed extract150 mg--

Other ingredients: Cellulose, Vegetable Stearate

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.
Brand IP Statement(s)

NSK-SD(TM) is a registered trademark of Japan BioScience Laboratories.

AmealPeptide(R) is a registered trademark of Calpis Co., Ltd

MegaNatural(R)-BP and the MegaNatural(R)-BP Logo are trademarks of Constellation Wines U.S., Inc.

General

Formula #200596

Precautions

Tamper resistant package, do not use if outer seal is missing.

Warning: Do not use if you are pregnant or breast feeding, if you are taking anticoagulant drugs (such as Warfarin) or other medications that effect blood clotting, or if you are at risk for any bleeding disorder.

KEEP OUT OF REACH OF CHILDREN.

Seals/Symbols

AmealPeptide(R) Clinically Proven

M MegaNatural(R)-BP(TM)

FDA Statement of Identity

A Dietary Supplement

Formulation

This product contains NO yeast, wheat, gluten, corn, sodium, sugar, starch, artificial coloring, preservatives or flavoring.

Suggested/Recommended/Usage/Directions

Suggested Usage: As a dietary supplement, adults take 4 capsules daily or as directed by your healthcare professional.

Storage

For optimal storage conditions, store in a cool, dry place. (59(0)-77(0)F/15(0)-25(0)C) (35-65% relative humidity)

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

See for yourself

Cardio-Stolix by Douglas Laboratories label

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

Cardio-Stolix 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 Cardio-Stolix by Douglas Laboratories

These are the 15 active ingredients this product is made of. Select any to open its full monograph.

Serving size4 Vegetarian 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.

Vitamin B6

Interacts with
210 drugs
10 mg per serving Form: Pyridoxine Hydrochloride

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

Folic Acid

Interacts with
40 drugs
800 mcg per serving

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when ta...

Folic Acid monograph & interactions

Calcium

Interacts with
168 drugs
50 mg per serving Form: Calcium Citrate

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 B12

Interacts with
20 drugs
500 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

L-Arginine

Interacts with
403 drugs
150 mg per serving Form: L-Arginine Hydrochloride

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for bl...

L-Arginine monograph & interactions

Hawthorn extract

Interacts with
191 drugs
250 mg per serving Form: Hyperoside, Vitexin-2-Rhamnoside

Hawthorn is a plant traditionally used for heart-related complaints, and some studies suggest it may modestly help symptoms of mild heart failure when...

Hawthorn extract monograph & interactions

Coleus extract

Interacts with
915 drugs
125 mg per serving Form: Forskolin

Coleus is a plant from the mint family whose root contains a compound called forskolin, often marketed for weight loss, asthma, and heart health. Whil...

Coleus extract monograph & interactions

Olive leaf extract

No known
interactions
75 mg per serving Form: Oleuropein

Olive comes from the same tree that gives us olives and olive oil, and its leaf and fruit contain antioxidant compounds like oleuropein and hydroxytyr...

Olive leaf extract monograph & interactions

Nattokinase

Interacts with
289 drugs
500 FU per serving Form: Soy

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at be...

Nattokinase monograph & interactions

Vitamin C

Interacts with
207 drugs
250 mg per serving Form: Magnesium Ascorbate, Potassium Ascorbate

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

Magnesium

Interacts with
295 drugs
100 mg per serving Form: Magnesium Ascorbate, magnesium taurinate

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preven...

Magnesium monograph & interactions

AmealPeptide(R) Hydrolyzed Casein

Interacts with
172 drugs
508 mg per serving Form: Milk

Casein peptides are small protein fragments made from milk casein, often studied for mild blood pressure support and relaxation. The evidence is limit...

AmealPeptide(R) Hydrolyzed Casein monograph & interactions

Valyl-Prolyl-Proline and Isoleucyl-Prolyl-Proline

3.4 mg per serving
  • › Valyl-Prolyl-Proline
  • › Isoleucyl-Prolyl-Proline

MegaNatural(R)-BP grape seed extract

Interacts with
910 drugs
150 mg per serving Form: Vitis vinifera

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and b...

MegaNatural(R)-BP grape seed extract monograph & interactions

Other (inactive) ingredients: Cellulose, Vegetable Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

Cardio-Stolix by Douglas Laboratories Drug Interactions

Want to check YOUR meds against Cardio-Stolix?

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
1,298Drugs
49 Major 1,239 Moderate 10 Minor

Ingredients driving the most interactions

Coleus extract 915
MegaNatural(R)-BP grape seed extract 910
L-Arginine 403
Magnesium 295
Nattokinase 289

Individual Drug Interactions

The ingredients in Cardio-Stolix interact with 1,298 drugs. Click any drug to see the details.

12 of the 15 ingredients in Cardio-Stolix interact with drugs. Each result below shows which ingredient is responsible. Coleus extract MegaNatural(R)-BP grape seed extract L-Arginine Magnesium Nattokinase Vitamin B6 Vitamin C Hawthorn extract AmealPeptide(R) Hydrolyzed Casein Calcium Folic Acid Vitamin B12

Each ingredient & the kinds of drugs it affects

For each ingredient in Cardio-Stolix 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.

Coleus extract7 drug types · 915 drugs

Calcium Channel Blockers

Theoretically, combining coleus with calcium channel blockers might increase the coronary vasodilatory effects.
Forskolin, a constituent of coleus, and calcium channel blockers both cause coronary vasodilatory effects.

Likelihood Probable Evidence B
Nitrates

Theoretically, combining coleus with nitrates might increase the coronary vasodilatory effects.
Forskolin, a constituent of coleus, and nitrates both cause coronary vasodilatory effects.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, concomitant use of coleus and anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
In vitro and animal research shows that forskolin, a constituent of coleus, can inhibit platelet aggregation and adhesion.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, combining coleus with antihypertensive drugs might cause additive blood pressure lowering effects and increase the risk of hypotension.
Animal research shows that forskolin, a constituent of coleus, may lower blood pressure.

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

Theoretically, taking coleus may affect drugs metabolized by CYP2C9 and increase the risk of adverse effects or reduce the effectiveness.
Research on the effect of coleus on CYP2C9 is conflicting. Some animal research shows that coleus extract can induce CYP2C9, while in vitro research shows that coleus can inhibit CYP2C9. Until more is known, advise patients that taking coleus might increase or decrease levels of drugs metabolized by CYP2C9.

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

Theoretically, taking coleus might decrease serum levels of drugs metabolized by CYP3A4.
In vitro research shows that coleus can activate the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of coleus and other drugs affected by these enzymes.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, taking coleus may affect the metabolism of warfarin and increase the risk of adverse effects or reduce the effectiveness.
Some animal research shows that coleus extract can induce cytochrome P450 2C9 (CYP2C9), an enzyme that metabolizes warfarin. However, other in vitro research shows that coleus can inhibit CYP2C9. Theoretically, taking coleus with drugs metabolized by CYP2C9 might affect drug levels and the risk of adverse effects. Until more is known, advise patients that taking coleus might increase or decrease levels of warfarin.

Likelihood Possible Evidence D
Coleus extract full monograph & interactions

MegaNatural(R)-BP grape seed extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

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

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

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

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

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

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D
MegaNatural(R)-BP grape seed extract full monograph & interactions

L-Arginine9 drug types · 403 drugs

Ace Inhibitors (Aceis)

Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.
Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects. Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.

Likelihood Probable Evidence D
Angiotensin Receptor Blockers (Arbs)

Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.
L-arginine increases nitric oxide, which causes vasodilation. Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation. Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
Preliminary research suggests that L-arginine infusions reduce platelet aggregation in humans. The clinical significance of this effect is unclear.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
Preliminary clinical research shows that L-arginine decreases blood glucose levels in patients with type 2 diabetes.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
L-arginine increases nitric oxide, which causes vasodilation. Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension. Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects.

Likelihood Probable Evidence D
Isoproterenol (Isuprel)

Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.
Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension.

Likelihood Probable Evidence D
Potassium-Sparing Diuretics

Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
Potassium-sparing diuretics can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.
In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation. Theoretically, concurrent use might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported.

Likelihood Possible Evidence D
Testosterone

Theoretically, concomitant use of L-arginine and testosterone might have additive effects.
In clinical research, L-arginine increases the level of testosterone in male patients with erectile dysfunction. The clinical significance of this finding is unclear.

Likelihood Possible Evidence D
L-Arginine full monograph & interactions

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Likelihood Possible Evidence D
Antacids

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

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

Magnesium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after magnesium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Likelihood Probable Evidence B
Calcium Channel Blockers

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Likelihood Possible Evidence D
Digoxin

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Likelihood Probable Evidence D
Quinolone Antibiotics

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Likelihood Probable Evidence A
Sulfonylureas

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

Likelihood Possible Evidence B
Magnesium full monograph & interactions

Nattokinase2 drug types · 289 drugs

Anticoagulant/Antiplatelet Drugs

Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
Nattokinase has thrombolytic and anticoagulant effects. There is a case report of intracranial hemorrhage in a patient who added nattokinase to aspirin therapy.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, nattokinase might increase the risk of hypotension when used with antihypertensive drugs.
Some clinical research suggests that nattokinase may reduce systolic and diastolic blood pressure.

Likelihood Possible Evidence D
Nattokinase full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

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
Vitamin C full monograph & interactions

Hawthorn extract6 drug types · 191 drugs

Nitrates

Theoretically, concomitant use might cause additive coronary vasodilatory effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Probable Evidence D
Phosphodiesterase-5 Inhibitors

Theoretically, concomitant use might result in additive vasodilation and hypotension.
Hawthorn might inhibit PDE-5 and cause vasodilation.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, hawthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that hawthorn can inhibit platelet aggregation. However, its effect in humans is unclear. One observational study shows that patients taking hawthorn shortly before undergoing coronary artery bypass graft (CABG) surgery or valve replacement surgery have a 10% incidence of postoperative bleeding, compared with 1% in those who never consumed hawthorn extract. However, clinical research shows that taking a specific preparation of dried hawthorn leaves and flowers (Crataesor, Soria Natural Lab) 800 mg three times daily for 15 days does not affect platelet aggregation or levels of thromboxane B2, the metabolite of thromboxane A2, in healthy humans.

Likelihood Possible Evidence D
Beta-Blockers

Theoretically, concomitant use might cause additive effects on blood pressure and heart rate.
Some evidence shows that hawthorn might lower blood pressure and heart rate.

Likelihood Possible Evidence D
Calcium Channel Blockers

Theoretically, concomitant use might cause additive coronary vasodilation and hypotensive effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, hawthorn might potentiate the effects and adverse effects of digoxin.
Hawthorn appears to improve cardiac output; however, hawthorn does not appear to affect digoxin pharmacokinetics. Case reports suggest that at least one species of hawthorn root extract (Crataegus mexicana) may produce adverse effects similar to digoxin and can cross-react with digoxin assays, leading to falsely elevated plasma digoxin levels.

Likelihood Possible Evidence D
Hawthorn extract full monograph & interactions

AmealPeptide(R) Hydrolyzed Casein1 drug type · 172 drugs

Antihypertensive Drugs

Theoretically, combining these casein peptides with antihypertensive drugs might increase the risk of hypotension.
Clinical research shows that some casein peptides, including the lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), can modestly reduce blood pressure in patients with hypertension.

Likelihood Probable Evidence B
AmealPeptide(R) Hydrolyzed Casein full monograph & 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

Folic Acid7 drug types · 40 drugs

5-Fluorouracil

Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil.

Likelihood Possible Evidence D
Capecitabine (Xeloda)

Use of high-dose folic acid might contribute to capecitabine toxicity.
Clinical research suggests that higher serum folate levels are associated with an increased risk for moderate or severe toxicity during capecitabine-based treatment for colorectal cancer. Additionally, in one case report, taking folic acid 15 mg daily might have contributed to increased toxicity, including severe diarrhea, vomiting, edema, hand-foot syndrome, and eventually death, in a patient prescribed capecitabine.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
Methotrexate exerts its cytotoxic effects by preventing conversion of folic acid to the active form needed by cells. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers. Advise cancer patients to consult their oncologist before using folic acid supplements. In patients treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis, folic acid supplements can reduce the incidence of side effects, without reducing efficacy.

Likelihood Probable Evidence B
Phenobarbital (Luminal)

Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin also reduces serum folate levels.

Likelihood Probable Evidence B
Primidone (Mysoline)

Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of primidone and worsening seizure control. Monitor closely for increased seizure activity. Note that primidone also reduces serum folate levels.

Likelihood Probable Evidence B
Pyrimethamine (Daraprim)

Folic acid might antagonize the effects of pyrimethamine.
Folic acid can antagonize the antiparasitic effects of pyrimethamine against toxoplasmosis and Pneumocystis carinii pneumonia. Folic acid doesn't antagonize the effects of pyrimethamine in the treatment of malaria, because malarial parasites cannot use exogenous folic acid. Use folinic acid as an alternative to folic acid when indicated.

Likelihood Probable Evidence D
Folic Acid 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 Cardio-Stolix, from the product label.

Douglas Laboratories

See all Douglas Laboratories products
Name
Douglas Laboratories
Street Address
600 Boyce Road
City
Pittsburgh
State
PA
ZipCode
15205
Phone Number
1.800.245.4440
Web Address
www.douglaslabs.com
Pharmacist Counseling Corner

Cardio-Stolix by Douglas Laboratories: Common Questions

Does Cardio-Stolix by Douglas Laboratories interact with any medications?
Yes. Based on its ingredients, Cardio-Stolix has a known interaction with 1,298 medications, including 49 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Cardio-Stolix contains 15 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.
Is Cardio-Stolix safe to take if I'm pregnant?
Most ingredients are considered likely safe at recommended doses — Vitamin B6, Folic Acid, Calcium, Vitamin B12, and Magnesium are all rated safe or likely safe in pregnancy. However, Hawthorn, Coleus, and Nattokinase are rated unsafe or possibly unsafe for pregnancy due to insufficient safety data. Talk with your doctor before starting, since the safety of the full combination and concentrated supplement forms isn't well established.
Can I take this while breastfeeding?
Vitamin B6, Folic Acid, Calcium, Vitamin B12, and Magnesium are considered likely safe at recommended amounts while breastfeeding. However, Hawthorn, Coleus, Olive leaf extract, and Nattokinase have insufficient or no safety data for breastfeeding, so they are best avoided unless your doctor advises otherwise. Check with your healthcare provider about the full product.
What does Hawthorn extract do in this product?
Hawthorn is a botanical traditionally used to support heart health and circulation — it may lower blood pressure and heart rate slightly. However, the evidence we hold is insufficient to rate whether it actually works for angina, arrhythmia, or other cardiovascular conditions. It does carry significant interaction risks with blood pressure drugs and certain heart medications.
What is Nattokinase and why is it in a cardiovascular product?
Nattokinase is an enzyme derived from fermented soy (natto) that has blood-thinning and clot-dissolving properties. It's included to theoretically support circulation and cardiovascular health, but the evidence we hold rates it as insufficient to confirm it works for angina, atherosclerosis, or heart disease. It does increase bleeding risk if you're on blood thinners.
What are the lactotripeptides (Valyl-Prolyl-Proline and Isoleucyl-Prolyl-Proline) for?
These peptides are derived from casein (milk protein) and have been studied for modest blood-pressure-lowering effects. They're included to support cardiovascular function. We could not check these specific peptides for drug interactions, so we hold no interaction data on them.
Will high doses of the vitamins in this product cause problems?
Yes. High-dose Vitamin B6 (especially above 1000 mg daily) can cause nerve damage (sensory neuropathy). High-dose Vitamin C can cause kidney stones and diarrhea. High-dose Magnesium can weaken bones over time. Stick to the recommended dose and talk with your pharmacist if you're considering adding extra supplements on top of this product.

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 Cardio-Stolix’s Ingredients

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

Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

Folic Acid

Interacts with 40 drugs

Folic acid is the man-made form of vitamin B9 and is one of the most well-studied supplements, especially for preventing serious birth defects when taken before and during early pregnancy. I...

Read the full Folic Acid 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 → 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

L-arginine

Interacts with 403 drugs

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for blood pressure, erectile dysfunction, and...

Read the full L-arginine monograph → Herb & supplement monograph

Hawthorn

Interacts with 191 drugs

Hawthorn is a plant traditionally used for heart-related complaints, and some studies suggest it may modestly help symptoms of mild heart failure when added to standard care. However, the ev...

Read the full Hawthorn monograph → Herb & supplement monograph

Coleus

Interacts with 915 drugs

Coleus is a plant from the mint family whose root contains a compound called forskolin, often marketed for weight loss, asthma, and heart health. While early lab and small human studies are...

Read the full Coleus monograph → Herb & supplement monograph

Olive

Olive comes from the same tree that gives us olives and olive oil, and its leaf and fruit contain antioxidant compounds like oleuropein and hydroxytyrosol. Olive oil as part of a Mediterrane...

Read the full Olive monograph → Herb & supplement monograph

Nattokinase

Interacts with 289 drugs

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulatio...

Read the full Nattokinase monograph → Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

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

Read the full Vitamin C monograph → Herb & supplement monograph

Magnesium

Interacts with 295 drugs

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preventing or correcting deficiency. Some othe...

Read the full Magnesium monograph → Herb & supplement monograph

Casein Peptides

Interacts with 172 drugs

Casein peptides are small protein fragments made from milk casein, often studied for mild blood pressure support and relaxation. The evidence is limited and mostly modest, so they should not...

Read the full Casein Peptides monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph →
Sources

Sources & How We Checked

Cardio-Stolix'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 469 references behind this product’s interaction data

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

Vitamin B6 32 references
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  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Folic Acid 56 references
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  2. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9. PubMed
  3. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41. PubMed
  4. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  5. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. PubMed
  6. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. PubMed
  7. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. PubMed
  8. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. PubMed
  9. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63.
  10. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease preventi
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  16. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  17. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78.
  18. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.
  19. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
  20. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
  21. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD000951. PubMed
  22. Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5. PubMed
  23. Schroder H, Clausen N, Ostergard E, Pressler T. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Ped Hematol Oncol 1986;3:241-7. PubMed
  24. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  25. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5. PubMed
  26. Bonaa KH, Njolstad I, Ueland PM, et al. NORVIT: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Enlg J Med 2006;354:1578-88. PubMed
  27. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  28. Figueiredo JC, Grau MV, Haile RW, et al. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432-5. PubMed
  29. Clippe C, Freyer G, Milano G, Trillet-Lenoir V. Lethal toxicity of capecitabine due to abusive folic acid prescription. Clin Oncol (R Coll Radiol) 2003;15:299-300. PubMed
  30. Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.
  31. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009;302:2119-26.
  32. Haberg, S. E., London, S. J., Stigum, H., Nafstad, P., and Nystad, W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis.Child 2009;94(3):180-184. PubMed
  33. Whitrow, M. J., Moore, V. M., Rumbold, A. R., and Davies, M. J. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol. 12-15-2009;170(12):1486-1493. PubMed
  34. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  35. Baggott, J. E., Oster, R. A., and Tamura, T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol. 2012;36(1):78-81. PubMed
  36. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  37. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  38. Taneja S, Strand TA, Kumar T, et al. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr 2013;98(3):731-7. PubMed
  39. van Wijngaarden JP, Swart KM, Enneman AW, et al. Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin
  40. Qin X, Fan F, Cui Y, Chen F, Chen Y, Cheng X, Li Y, Wang B, Xu X, Xu X, Huo Y, Wang X. Folic acid supplementation with and without vitamin B6 and revascularization risk: a meta-analysis of randomized controlled trials. Clin Nutr. 2014;33(4):603-12. PubMed
  41. Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(5):1272-81. PubMed
  42. Matsubara S, Imai K, Murayama K, Higashizawa T. Severe liver dysfunction during nausea and vomiting of pregnancy: folic acid supplement as a suggested culprit. J Obstet Gynaecol. 2012;32(7):701-2. PubMed
  43. Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, Wang X. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer. 2013 1;133(5):1033-41. PubMed
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  46. Valera-Gran D, García de la Hera M, Navarrete-Muñoz EM, Fernandez-Somoano A, Tardón A, Julvez J, Forns J, Lertxundi N, Ibarluzea JM, Murcia M, Rebagliato M, Vioque J; Infancia y Medio Ambiente (INMA) Project. Folic acid supplements during pregnancy and ch
  47. Van Der Woude DA, De Vries J, Van Wijk EM, Verzijl JM, Pijnenborg JM. A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia. Int J Gynaecol Obstet. 2014;126(2):101-5. PubMed
  48. Vila-Nova C, Wehby GL, Queirós FC, Chakraborty H, Félix TM, Goco N, Moore J, Gewehr EV, Lins L, Affonso CM, Murray JC. Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil. J Perinat Med. 201 PubMed
  49. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bønaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland PM, Bennett D, Collins R, Peto R; B-V
  50. Wehby GL, Félix TM, Goco N, Richieri-Costa A, Chakraborty H, Souza J, Pereira R, Padovani C, Moretti-Ferreira D, Murray JC. High dosage folic acid supplementation, oral cleft recurrence and fetal growth. Int J Environ Res Public Health. 2013 4;10(2):590-6 PubMed
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See these in context on the Folic Acid monograph →

Calcium 62 references
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Coleus 16 references
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Olive 2 references
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Casein Peptides 4 references
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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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