Major interaction on record — check this product against your medications before combining. Based on 14 of 17 ingredients. Check your meds →
Dietary supplement

Dothelle DHA Softgels Ingredients & Drug Interactions

by Method Pharmaceuticals

Dothelle DHA Softgels label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 23, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Dothelle DHA Softgels 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

Dothelle DHA Softgels is a dietary supplement by Method Pharmaceuticals with 17 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,215 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Vitamin B3, Omega-3 Fatty Acids, Magnesium. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Dothelle DHA Softgels by Method Pharmaceuticals

Ask about any prescription or over-the-counter medication and we check it for interactions with Dothelle DHA Softgels by Method Pharmaceuticals — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Dothelle DHA Softgels by Method Pharmaceuticals

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 23, 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 16 of its 24 active ingredients.
  • “Vitamin C” is listed as a grouped ingredient — the label gives one combined amount (25 mg) without saying how much of each component you get.
  • “Omega-3 Fatty Acids” is listed as a grouped ingredient — the label gives one combined amount (200 mg) without saying how much of each component you get.
  • “Flavonoids” is listed as a grouped ingredient — the label doesn't break down how much of each component you get.

Dothelle DHA Softgels contains 24 ingredients, with active vitamins and minerals including B vitamins (B1, B2, B3, B5, B6, B7, and B12), vitamin C, calcium, copper, magnesium, potassium, and zinc; omega-3 fatty acids (fish oil); and supporting compounds like glutathione, hesperidin, lysine, and iron. The product has no reported inactive other ingredients.

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: Prenatal vitamin with omega-3 fatty acid supplement.
  • We looked for evidence on: Anemia, Anemia of chronic disease, Fetal development support, Maternal nutrition during pregnancy, Prenatal micronutrient supplementation.
  • The strongest evidence on file: Iron is rated "Effective" for Anemia of chronic disease (Natural Medicines).
  • Also on file: Iron is rated "Effective" for Iron deficiency anemia.
  • Also on file: Vitamin B6 is rated "Effective" for Sideroblastic anemia.

The data show that individual ingredients have varying levels of evidence. Vitamin B6 is effective for sideroblastic anemia and B6 deficiency, and likely effective for high homocysteine (hyperhomocysteinemia).

Folic acid is effective for folate deficiency and likely effective for preventing neural tube birth defects and treating methotrexate toxicity. Vitamin B12 is effective for B12 deficiency.

Fish oil is effective for high triglycerides (hypertriglyceridemia) and possibly effective for heart failure and nonalcoholic fatty liver disease. Iron is effective for iron deficiency anemia and pregnancy-related iron deficiency.

Magnesium is effective for constipation. Calcium is effective for kidney failure and osteoporosis.

Other ingredients carry ratings from possibly effective to insufficient evidence—the product facts we hold do not establish that the combination as a whole is effective for any particular condition.

The evidence, ingredient by ingredient Vitamin B6 Folic Acid Vitamin B12 Vitamin C Glutathione Docosahexaenoic Acid (dha) Fish Oil Riboflavin

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 18 of the 18 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 18 of 18.
  • General safety write-ups exist for 18 of 18.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at recommended doses. Vitamin B6 is safe at normal food and supplement amounts but can cause nerve damage (sensory neuropathy) at high doses over time or total doses above 1,000 grams.

Folic acid is generally safe; vitamin B12 is very safe with no established upper limit because excess is removed in urine. Fish oil is well tolerated but may increase bleeding risk at doses above 3 grams daily and can cause fishy aftertaste, loose stools, and nausea.

Iron is well tolerated at appropriate doses but can cause constipation, diarrhea, and stomach upset. Magnesium commonly causes diarrhea and nausea.

Zinc may cause nausea, diarrhea, and metallic taste. Niacin can cause flushing (up to 70% of users), gastrointestinal upset, and liver enzyme changes.

Hesperidin has limited long-term safety data. Glutathione is orally well tolerated short-term but long-term safety is unclear.

Copper is safe in food and standard supplements but excess can be toxic. For pregnancy and breastfeeding: vitamin B6 is likely safe in pregnancy but possibly unsafe—discuss with your doctor; folic acid is likely safe and recommended for birth defect prevention; B12 is likely safe and needed; fish oil is likely safe but possibly unsafe—check with your provider; iron is likely safe but possibly unsafe; magnesium is likely safe but possibly unsafe; calcium is likely safe but possibly unsafe; niacin is likely safe; biotin and niacinamide are likely safe.

Glutathione has insufficient safety information and should be avoided in pregnancy and breastfeeding unless your doctor advises otherwise. Hesperidin lacks sufficient safety data for pregnancy and breastfeeding.

Lysine has no pregnancy/lactation data on file.

Side effects, ingredient by ingredient Vitamin B6 Folic Acid Vitamin B12 Vitamin C Glutathione Docosahexaenoic Acid (dha) Fish Oil Riboflavin

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?
  • 16 of the 18 matched ingredients can interact with medications — Lysine, Calcium, Potassium, Copper, Iron, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,180 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 Dothelle DHA Softgels, double-check with your doctor or pharmacist if you take levodopa/carbidopa (Parkinson's disease)—magnesium can sharply reduce its effect. Also verify your use of seizure medications (phenytoin, phenobarbital, primidone), blood thinners or anticoagulants (warfarin), blood pressure drugs (antihypertensives), HIV integrase inhibitors (dolutegravir, elvitegravir), cancer medications (methotrexate, capecitabine, cisplatin), antibiotics (quinolones, tetracyclines, cephalexin, ceftriaxone), thyroid medications (levothyroxine), or immunosuppressants (tacrolimus, cyclosporine).

Moderate-severity interactions also exist with antidiabetes drugs, heart rhythm medications (amiodarone, calcium channel blockers, sotalol), lithium, and others.

Check your own medication Run your meds through the checker above

The bottom line

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

This is a multivitamin and mineral product with fish oil, most useful if you have a documented deficiency in one or more of its ingredients or are seeking omega-3 intake. Because of its vitamin B6, folic acid, and especially its magnesium and calcium content, it has multiple documented interactions with common medications—particularly seizure drugs, blood pressure and heart medications, blood thinners, antibiotics, thyroid drugs, and HIV medications.

If you take any prescription medication or manage a chronic condition, check your specific drugs using the tool on this page before starting, and discuss the result with your doctor or pharmacist.

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

Assessment coverage: 20 of 24 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 18, 2021.

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 Dothelle DHA Softgels, straight from the product label.

Brand Method Pharmaceuticals
Barcode (UPC) 358657121303
Net contents 30 Capsule(s)
Market status On market
Date entered into DSLD Dec 18, 2021
DSLD ID 263294
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses Nutrient, All Other
Intended target group(s) Adult (18 - 50 Years), Pregnant Women
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 Dothelle DHA Softgels by Method Pharmaceuticals, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Pregnant and Lactating
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
Servings per container
30
UPC/BARCODE
358657121303
IngredientAmount% DV
Vitamin B625 mg1000%
Folic Acid1 mg125%
Vitamin B1212.5 mcg156%
Vitamin C25 mg42%
Omega-3 Fatty Acids200 mg--
Glutathione0 NP--
Fish Oil310 mg--
Vitamin B12 mg118%
Vitamin B23 mg150%
Flavonoids0 NP--
Hesperidin0 NP--
Copper2 mg100%
Sodium Ascorbate0 NP--
Zinc10 mg67%
Vitamin B31.8 mg9%
Vitamin B55 mg50%
Magnesium5 mg1%
Magnesium Ascorbate0 NP--
Vitamin B7300 mcg100%
Potassium Ascorbate0 NP--
Calcium Ascorbate0 NP--
Niacinamide Ascorbate0 NP--
Lysine Acetate0 NP--
Ferrous Fumarate53.5 mg--
Polysaccharide Iron Complex38 mg194%
Ascorbic Acid Precursors0 NP--
Acid Metabolites0 NP--
Basic Amino Acids0 NP--
DHA156 mg--
EPA39 mg--

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.
Formula

Description: Dothelle DHA is a prescription prenatal vitamin-mineral preparation containing omega-3 fatty acid supplements. The Dothelle DHA capsule is an oval, blue soft gelatin capsule, and is imprinted with "M121".

Dothelle DHA Softgels with ascorbic acid precursors

Suggested/Recommended/Usage/Directions

Recommended Use: Adults (persons over 12 years of age), One (1) capsule daily, between meals, or as prescribed by physician. Do not exceed recommended dosage. Do not administer to children under the age of 12.

Precautions

Do not exceed recommended dosage.

Do not administer to children under the age of 12.

Warning: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

Call your doctor about side effects. You may report side effects by calling 877-250-3427.

Keep out of reach of children.

Storage

Storage: Store at 20 degrees-25 degrees C (68 degrees-77 degrees F), excursions permitted to 15 degrees-30 degrees C (59 degrees-86 degrees F) [See USP controlled room temperature].

General Statements

58657-121-30

Rx

FDA Statement of Identity

Prenatal Multivitamin Supplement

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

See for yourself

Dothelle DHA Softgels by Method Pharmaceuticals label

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

Dothelle DHA Softgels 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 Dothelle DHA Softgels by Method Pharmaceuticals

These are the 17 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 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
25 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
1 mg 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

Vitamin B12

Interacts with
20 drugs
12.5 mcg per serving Form: Cyanocobalamin

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

Vitamin C

Interacts with
207 drugs
25 mg per serving

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
  • › Glutathione
  • › Flavonoids
  • › Ascorbic Acid Precursors
  • › Basic Amino Acids

Omega-3 Fatty Acids

Interacts with
375 drugs
200 mg per serving

DHA is an omega-3 fatty acid found in fatty fish and algae that is a building block for the brain, nervous system, and eyes. It is widely used and gen...

Omega-3 Fatty Acids monograph & interactions

Vitamin B1

2 mg per serving Form: Thiamine Mononitrate

Vitamin B2

Interacts with
20 drugs
3 mg per serving Form: Riboflavin

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally...

Vitamin B2 monograph & interactions

Copper

Interacts with
31 drugs
2 mg per serving Form: Copper Sulfate

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes wor...

Copper monograph & interactions

Zinc

Interacts with
67 drugs
10 mg per serving Form: Zinc Sulfate

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but suppleme...

Zinc monograph & interactions

Vitamin B3

Interacts with
727 drugs
1.8 mg per serving

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

Vitamin B3 monograph & interactions

Vitamin B5

5 mg per serving Form: D-Calcium Pantothenate

Magnesium

Interacts with
295 drugs
5 mg per serving Form: Magnesium Sulfate

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

Vitamin B7

No known
interactions
300 mcg per serving Form: Biotin

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get...

Vitamin B7 monograph & interactions

Ferrous Fumarate

Interacts with
80 drugs
53.5 mg per serving Form: Ferrous Fumarate Anhydrous

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventin...

Ferrous Fumarate monograph & interactions

Polysaccharide Iron Complex

Interacts with
80 drugs
38 mg per serving

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventin...

Polysaccharide Iron Complex monograph & interactions

DHA

156 mg per serving

EPA

39 mg per serving
Interaction report

Dothelle DHA Softgels by Method Pharmaceuticals Drug Interactions

Want to check YOUR meds against Dothelle DHA Softgels?

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
1,215Drugs
13 Major 1,195 Moderate 7 Minor

Ingredients driving the most interactions

Vitamin B3 727
Omega-3 Fatty Acids 375
Magnesium 295
Vitamin B6 210
Vitamin C 207

Individual Drug Interactions

The ingredients in Dothelle DHA Softgels interact with 1,215 drugs. Click any drug to see the details.

11 of the 17 ingredients in Dothelle DHA Softgels interact with drugs. Each result below shows which ingredient is responsible. Vitamin B3 Omega-3 Fatty Acids Magnesium Vitamin B6 Vitamin C Ferrous Fumarate Zinc Folic Acid Copper Vitamin B12 Vitamin B2

Each ingredient & the kinds of drugs it affects

For each ingredient in Dothelle DHA Softgels 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.

Vitamin B315 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
Vitamin B3 full monograph & interactions

Omega-3 Fatty Acids3 drug types · 375 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, DHA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Although some clinical evidence suggests that DHA might reduce collagen-stimulated platelet aggregation and thromboxane release, most clinical evidence suggests that DHA alone does not affect blood clotting. However, theoretically, when given in combination with EPA as fish oil, concomitant use with anticoagulant or antiplatelet drugs (including aspirin) might increase risk of bleeding.

Likelihood Unlikely Evidence B
Antidiabetes Drugs

Theoretically, taking DHA with antidiabetes drugs might reduce the effects of these medications.
In people with type 2 diabetes, including those taking oral hypoglycemic medications, DHA seems to increase fasting blood glucose levels.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking DHA with antihypertensive drugs might increase the risk of hypotension.
Fish oils containing DHA can lower blood pressure and might have additive effects in patients treated with antihypertensives; use with caution.

Likelihood Probable Evidence B
Omega-3 Fatty Acids 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

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

Ferrous Fumarate13 drug types · 80 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Iron 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 iron 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, iron containing products.

Likelihood Probable Evidence D
Bisphosphonates

Iron reduces the absorption of bisphosphonates.
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Denosumab (Prolia, Others)

Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other.

Likelihood Possible Evidence D
Dolutegravir (Tivicay)

Iron might decrease dolutegravir levels by reducing its absorption.
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54%.

Likelihood Probable Evidence B
Integrase Inhibitors

Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation. One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation. Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation.

Likelihood Possible Evidence D
Levodopa

Iron might decrease levodopa levels by reducing its absorption.
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50%. The clinical significance of this hasn't been determined.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Iron might decrease levothyroxine levels by reducing its absorption.
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence B
Methyldopa (Aldomet)

Iron might decrease methyldopa levels by reducing its absorption.
Advise patients to separate methyldopa and iron doses by at least 2 hours. Iron can decrease the absorption of methyldopa from the gastrointestinal tract through chelation, resulting in increases in blood pressure.

Likelihood Probable Evidence B
Mycophenolate Mofetil (Cellcept)

Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research.

Likelihood Unlikely Evidence D
Penicillamine (Cuprimine, Depen)

Iron might decrease penicillamine levels by reducing its absorption.
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine.

Likelihood Probable Evidence D
Quinolone Antibiotics

Iron might decrease levels of quinolone antibiotics by reducing their absorption.
Advise patients to separate quinolone antibiotics and iron doses by at least 2 hours. Iron decreases the absorption of quinolones due to formation of insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90%.

Likelihood Probable Evidence D
Chloramphenicol

Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Chloramphenicol interferes with erythrocyte maturation. However, since chloramphenicol isn't usually taken for prolonged periods, this isn't likely to be clinically significant.

Likelihood Unlikely Evidence D
Ferrous Fumarate full monograph & interactions

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Theoretically, zinc 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 zinc containing products.

Likelihood Probable Evidence D
Cephalexin (Keflex)

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Likelihood Possible Evidence D
Integrase Inhibitors

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Likelihood Probable Evidence B
Quinolone Antibiotics

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Likelihood Probable Evidence B
Ritonavir (Norvir)

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Likelihood Probable Evidence B
Amiloride (Midamor)

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Likelihood Probable Evidence B
Atazanavir (Reyataz)

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Likelihood Probable Evidence B
Zinc 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

Copper2 drug types · 31 drugs

Penicillamine (Cuprimine, Depen)

Theoretically, taking copper with penicillamine might decrease the absorption of penicillamine; separate dosing by at least 2 hours.
Copper chelates penicillamine, which decreases its absorption and may reduce its clinical effects.

Likelihood Probable Evidence D
Contraceptive Drugs

Theoretically, taking copper with contraceptive drugs might increase the levels and toxic effects of copper.
A meta-analysis of clinical studies suggests that chronic use of oral contraceptives increases serum copper levels by a mean of 57 mcg/dL. In most people, this resulted in levels above the normal reference range for copper.

Likelihood Possible Evidence D
Copper 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

Vitamin B21 drug type · 20 drugs

Tetracycline Antibiotics

Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.

Likelihood Possible Evidence D
Vitamin B2 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Dothelle DHA Softgels, from the product label.

Method Pharmaceuticals

See all Method Pharmaceuticals products
Name
Method Pharmaceuticals, LLC
City
Arlington
State
TX
ZipCode
76006
Pharmacist Counseling Corner

Dothelle DHA Softgels by Method Pharmaceuticals: Common Questions

Does Dothelle DHA Softgels by Method Pharmaceuticals interact with any medications?
Yes. Based on its ingredients, Dothelle DHA Softgels has a known interaction with 1,215 medications, including 13 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Dothelle DHA Softgels contains 17 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take Dothelle DHA if I'm pregnant?
Most ingredients are safe in pregnancy at normal dietary and prenatal supplement amounts: folic acid is recommended to prevent birth defects, and B vitamins, iron, and calcium support pregnancy needs. However, vitamin B6 is possibly unsafe and fish oil, magnesium, and calcium carry some uncertainty. Talk with your prenatal care provider about whether this specific product is right for you and what dose to use.
Is there fish in this product, and could I have an allergic reaction?
Yes, this product contains fish oil. Case reports exist of anaphylaxis in people with shellfish allergies taking fish oil supplements. If you have a fish or shellfish allergy, discuss with your doctor or pharmacist before using this product.
What is DHA and why is it in a multivitamin?
DHA (docosahexaenoic acid) is an omega-3 fatty acid found in fish oil that supports brain and eye health. The product's name reflects its fish oil content, which is included alongside vitamins and minerals to provide comprehensive nutritional support.
Can taking this with my blood pressure medication make my blood pressure too low?
Possibly. Vitamin B6, fish oil, hesperidin, and niacin in this product can all lower blood pressure, and magnesium may have additive effects with blood pressure drugs. If you're on antihypertensive medication, check your specific drugs with the tool on this page and review the result with your doctor or pharmacist before starting.
I take metformin for diabetes. Can I use this product?
Metformin may lower vitamin B12 levels over time, and this product contains B12—which is good. However, niacin in the product can raise blood sugar and interfere with diabetes control. Review your medications on this page and discuss with your doctor or pharmacist before starting.
Will the iron in this interfere with my thyroid medication?
Yes, iron can reduce levothyroxine (Synthroid) absorption by 30–50%. If you take thyroid medication, separate iron from your thyroid drug by at least 2 hours and discuss the timing with your pharmacist to ensure your thyroid medication stays effective.

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

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The Full Monographs Behind Dothelle DHA Softgels’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

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

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

Glutathione

Glutathione is a powerful antioxidant your body makes naturally, and many people take it as a supplement hoping for skin, detox, or anti-aging benefits. However, strong human evidence is lim...

Read the full Glutathione monograph → Herb & supplement monograph

Docosahexaenoic Acid (dha)

Interacts with 375 drugs

DHA is an omega-3 fatty acid found in fatty fish and algae that is a building block for the brain, nervous system, and eyes. It is widely used and generally well tolerated, with the stronges...

Read the full Docosahexaenoic Acid (dha) monograph → Herb & supplement monograph

Fish Oil

Interacts with 327 drugs

Fish oil provides omega-3 fatty acids (EPA and DHA) that are best known for lowering high triglyceride levels. The evidence for other heart and health benefits is mixed, and it is generally...

Read the full Fish Oil monograph → Herb & supplement monograph

Riboflavin

Interacts with 20 drugs

Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally very safe at typical doses, and the stro...

Read the full Riboflavin monograph → Herb & supplement monograph

Copper

Interacts with 31 drugs

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes work. Most people get enough copper from fo...

Read the full Copper monograph → Herb & supplement monograph

Zinc

Interacts with 67 drugs

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a defici...

Read the full Zinc 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

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

Biotin

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get plenty from a normal diet, and true defi...

Read the full Biotin monograph → Herb & supplement monograph

Iron

Interacts with 80 drugs

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventing iron deficiency and iron-deficiency an...

Read the full Iron monograph →
Sources

Sources & How We Checked

Dothelle DHA Softgels'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 859 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
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  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
  11. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4. PubMed
  12. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  13. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
  14. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31. DOI
  15. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94. PubMed
  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
  44. Tio M, Andrici J, Cox MR, Eslick GD. Folate intake and the risk of prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17(3):213-9. PubMed
  45. Tomaszewski JJ, Richman EL, Sadetsky N, O'Keefe DS, Carroll PR, Davies BJ, Chan JM. Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE. J Urol. 2014;191(4):971-6. PubMed
  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
  51. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  52. Liu J, Li Z, Ye R, Liu J, Ren A. Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4-6 years of age. ERJ Open Res. 2020;6(1):00250-2019. PubMed
  53. Houghton LA, Sherwood KL, Pawlosky R, Ito S, O'Connor DL. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr. 2006 Apr;83(4):842-50. PubMed
  54. Houghton LA, Yang J, O'Connor DL. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr. 2009 Jan;89(1):216-20. PubMed
  55. Chan SL, Chan AWH, Mo F, et al. Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer. Oncologist. 2018 Dec;23(12):1436-1445. PubMed
  56. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T

See these in context on the Folic Acid monograph →

Vitamin B12 30 references
  1. 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
  2. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. DOI
  3. 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..
  4. 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
  5. 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
  6. Geissbuhler, P., Mermillod, B., and Rapin, C. H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: a prospective study over five years. J.Pain Symptom.Manage. 2000;20(2):93-103. PubMed
  7. Salles, N., Herrmann, F., Sakbani, K., Rapin, C. H., and Sieber, C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr.Soc 2005;53(5):917-918.
  8. Looker, H. C., Fagot-Campagna, A., Gunter, E. W., Pfeiffer, C. M., Sievers, M. L., Bennett, P. H., Nelson, R. G., Hanson, R. L., and Knowler, W. C. Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res R
  9. Uhl, W., Nolting, A., Golor, G., Rost, K. L., and Kovar, A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila) 2006;44 Suppl 1:17-28. PubMed
  10. Borron, S. W., Baud, F. J., Barriot, P., Imbert, M., and Bismuth, C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg.Med 2007;49(6):794-801, 801. PubMed
  11. Borron, S. W., Baud, F. J., Megarbane, B., and Bismuth, C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg.Med 2007;25(5):551-558. PubMed
  12. Lewis, J. G. Gout, Steatorrhoea, and Megaloblastic Anaemia. Ann Rheum.Dis 1962;21(3):284-286. PubMed
  13. Tal, S., Shavit, Y., Stern, F., and Malnick, S. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr.Soc 2010;58(3):523-526. PubMed
  14. Baztan, J. J., Gavidia, J. J., Gomez-Pavon, J., Esteve, A., and Ruiperez, I. High vitamin B12 levels and in-hospital mortality. J Am Geriatr.Soc 2010;58(11):2237-2238. PubMed
  15. Omboni, E., Checchini, M., and Longoni, F. [Hypopotassemia and megaloblastic anemia. Presentation of a case]. Minerva Med 8-31-1987;78(16):1255-1257.
  16. Aalfs As, Scholvinck LH, Horvath B. Acneiform eruption in a 5-year old due to vitamin B12 supplementation. Eur J Dermatol 2013;23(5):726-7. PubMed
  17. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan Ocul Toxicol 2014;33(2):94-5. PubMed
  18. Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emerg Care 2013;29(11):1223-4. PubMed
  19. Djuric V, Bogic M, Popadic AP, et al. Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin. Ann Allergy Asthma Immunol 2012;108(3):207-8. PubMed
  20. Kartel O, Gulec M, Demirel F, et al. Vitamin B12 allergy and successful desensitization with cyanocobalamin: A case report. Allergol Immunopath (Madr) 2012;40(5):324-5.
  21. Patiroglu T, Unal E, Yildirim S. Infantile tremor syndrome associated with cobalamin therapy: A case report. Clin Neurol Neurosurg 2013;115(9):1903-5. PubMed
  22. Schulte S, Barkema LW, Kardaun SH. Long-lasting atypical acneiform eruption with prominent comedones induced by hydroxocobalamin (vitamin B12). J Dtsch Dermatol Ges 2014;12(6):502-3.
  23. Zanus C, Alberini E, Costa P, et al. Involuntary movements after correction of vitamin B12 deficiency: A video-case report. Epileptic Disord 2012;14(2):174-80. PubMed
  24. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  25. Fujita Y, Mizukami T, Maya Y, et al. Vitamin B12 allergy manifesting as lymphomatoid contact dermatitis. Eur J Dermatol. 2020;30(3):304-305. PubMed
  26. Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Crit Care. 2019;23(1):421. PubMed
  27. Khairan P, Sobue T, Eshak ES, et al. Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study. BMC Cancer 2021;21(1):982. PubMed
  28. Evans J, Pandya A, Ding Y, Qunibi WY. Hydroxocobalamin-Induced Oxalate Nephropathy in a Patient With Smoke Inhalation. Kidney Int Rep 2021;6(8):2228-2231. PubMed
  29. Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Sci Rep 2021;11(1):13361. PubMed
  30. Pegalajar-García MD, Cebolla-Verdugo M, Prados-Carmona Á, Llamas-Segura C, Navarro-Triviño FJ. Systemic allergic dermatitis to cobalt present in cyanocobalamin supplementation. Contact Dermatitis 2023;89(3):203-205. PubMed

See these in context on the Vitamin B12 monograph →

Vitamin C 51 references
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Docosahexaenoic Acid (dha) 49 references
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Glutathione 1 reference
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Fish Oil 157 references
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Hesperidin 14 references
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Copper 11 references
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Biotin 4 references
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Potassium 12 references
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Niacinamide 22 references
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Iron 72 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.

© 2021 Therapeutic Research Center, LLC

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