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Dietary supplement

The Ultimate AntiOxidant Formula Ingredients & Drug Interactions

by Natrol

The Ultimate AntiOxidant Formula label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking The Ultimate AntiOxidant Formula 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

The Ultimate AntiOxidant Formula is a dietary supplement by Natrol with 17 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis prevention, dietary calcium deficiency, heartburn relief (calcium carbonate antacids).Based on those ingredients, 1,577 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Turmeric, Milk Thistle, Grape. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against The Ultimate AntiOxidant Formula by Natrol

Ask about any prescription or over-the-counter medication and we check it for interactions with The Ultimate AntiOxidant Formula by Natrol — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of The Ultimate AntiOxidant Formula by Natrol

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 11, 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 11 of its 17 active ingredients.
  • “Flavonoid extract” is listed as a grouped ingredient — the label gives one combined amount (200 mg) without saying how much of each component you get.

The Ultimate AntiOxidant Formula contains 17 active ingredients: vitamins A, C, and E; minerals calcium, selenium, zinc, and copper; niacin; and plant extracts including milk thistle, turmeric, hawthorn, grape, spirulina (blue-green algae), calendula, artichoke, and bilberry. Inactive ingredients are gelatin capsule, silica, dibasic calcium phosphate, sucrose, ethyl cellulose, hypromellose, soybean oil, and magnesium stearate.

Does it work?

Not established
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
Not established

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: fight free radicals and boost immunity.
  • We looked for evidence on: Anxiety, Arrhythmia, Atherosclerosis, Atopic dermatitis (eczema), Antioxidant support, Immune function — and 1 related terms.
  • The closest evidence on file: Vitamin E is rated "Possibly Ineffective" for Atherosclerosis (Natural Medicines).
  • Also on file: Vitamin E is rated "Possibly Ineffective" for Atopic dermatitis (eczema).
  • Also on file: Vitamin C is rated "Possibly Ineffective" for Atherosclerosis.

The evidence for effectiveness varies widely by ingredient. Calcium is effective for kidney failure, dyspepsia, low blood calcium, and high potassium, and likely effective for osteoporosis.

Niacin is likely effective for pellagra and possibly effective for metabolic syndrome and certain lipid disorders related to HIV. Vitamins C and E are effective for their respective deficiencies; vitamin E is possibly effective for Alzheimer's disease, while vitamin C may help with age-related macular degeneration and certain infections.

Zinc is effective for zinc deficiency and likely effective for Wilson disease. Selenium is likely effective for selenium deficiency and possibly effective for Kashin-Beck disease and pre-eclampsia.

Milk thistle is possibly effective for diabetes. Turmeric is possibly effective for depression and high cholesterol.

Several other ingredients—hawthorn, grape, vitamin A, spirulina, calendula, artichoke, bilberry—show insufficient reliable evidence or mixed findings. For many conditions listed, the evidence is insufficient to establish benefit.

The evidence, ingredient by ingredient Calcium Niacin Vitamin E Vitamin C Selenium Vitamin A Blue-green Algae Calendula

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 17 of the 17 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 17 of 17.
  • General safety write-ups exist for 17 of 17.
  • 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. Calcium is safe in appropriate amounts and important in pregnancy and breastfeeding, though very high doses can cause kidney stones and calcification problems.

Niacin from food is safe; high-dose supplements can cause flushing, liver problems, and gastrointestinal upset, and should be avoided in pregnancy at high doses. Vitamin E is generally well tolerated but high-dose long-term supplements may raise bleeding risk.

Vitamin C is safe at normal dietary amounts; very high doses can cause kidney stones and stomach upset. Vitamin A at recommended levels is safe; high doses—especially retinol forms—can cause birth defects and should be avoided in pregnancy.

Selenium, zinc, and copper are safe in recommended amounts; excess amounts of any can be toxic. Milk thistle should be avoided in pregnancy due to insufficient safety data.

Turmeric, hawthorn, and spirulina have limited pregnancy/breastfeeding safety data and are best avoided during these times unless directed by a doctor. Calendula, artichoke, and bilberry also lack sufficient pregnancy data.

Side effects, ingredient by ingredient Calcium Niacin Vitamin E Vitamin C Selenium Vitamin A Blue-green Algae Calendula

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?
  • 17 of the 17 matched ingredients can interact with medications — Milk Thistle, Bilberry, Calendula, Grape, Hawthorn, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,578 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Check with your pharmacist before taking this product if you take blood thinners (warfarin, Coumadin, or anticoagulants and antiplatelet drugs), HIV medications (integrase inhibitors like dolutegravir or elvitegravir, or protease inhibitors like ritonavir), blood pressure medications, birth control or hormone therapy, diabetes drugs, antibiotics (especially quinolones, tetracyclines, or cephalexin), gout treatments (allopurinol, probenecid), chemotherapy drugs, or thyroid medication (levothyroxine).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with no established evidence rating for its marketed use. Major medication interactions have been identified, and safety information is well characterized.

This product is an antioxidant blend that may benefit people with specific deficiencies or those seeking general antioxidant support, though the evidence for antioxidant benefit in healthy people is mixed. Anyone taking medications—especially blood thinners, birth control, blood pressure drugs, diabetes medications, antibiotics, or cancer treatments—should check their specific drugs against the interaction tool before starting.

Pregnant or breastfeeding individuals should discuss this product with their pharmacist or doctor given the pregnancy cautions on several ingredients.

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

Assessment coverage: 17 of 17 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 24, 2017.

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 The Ultimate AntiOxidant Formula, straight from the product label.

Brand Natrol
Net contents 60 Capsule(s)
Market status On market
Date entered into DSLD Feb 24, 2017
DSLD ID 71075
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for The Ultimate AntiOxidant Formula by Natrol, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
30
IngredientAmount% DV
Calcium28 mg3%
Niacin40 mg200%
Vitamin E200 IU667%
Vitamin C250 mg417%
Selenium125 mcg179%
Milk Thistle0 NP--
Rose Hips0 NP--
Turmeric0 NP--
Hawthorn0 NP--
Grape0 NP--
Vitamin A10000 IU200%
Spirulina300 mg--
Calendula powder50 mg--
Artichoke 4:1 extract50 mg--
Zinc25 mg167%
Copper2 mg100%
Flavonoid extract200 mg--
Bilberry0 NP--

Other ingredients: Gelatin, Silica, Dibasic Calcium Phosphate, Sucrose, Ethyl Cellulose, Hypromellose, Soybean Oil, Magnesium Stearate

Tap any ingredient to jump to its full detail below.

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

Over 5 super-powered antioxidants

General Statements

Fight free radicals and boost immunity

FDA Statement of Identity

Dietary Supplement

FDA Disclaimer Statement

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

Suggested/Recommended/Usage/Directions

Directions: Take 2 capsules, one time daily, with a meal.

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

See for yourself

The Ultimate AntiOxidant Formula by Natrol label

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

The Ultimate AntiOxidant Formula 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 The Ultimate AntiOxidant Formula by Natrol

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

Serving size2 Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

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

Calcium

Interacts with
168 drugs
28 mg per serving Form: Calcium Ascorbate

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

Calcium monograph & interactions

Niacin

Interacts with
727 drugs
40 mg per serving Form: Niacinamide

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

Niacin monograph & interactions

Vitamin E

Interacts with
764 drugs
200 IU per serving Form: D-Alpha-Tocopheryl Succinate

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correc...

Vitamin E monograph & interactions

Vitamin C

Interacts with
207 drugs
250 mg per serving Form: Calcium Ascorbate

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

Vitamin C monograph & interactions

Selenium

Interacts with
321 drugs
125 mcg per serving Form: L-Selenomethionine

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...

Selenium monograph & interactions

Vitamin A

Interacts with
387 drugs
10000 IU per serving Form: natural Beta-Carotene

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplemen...

Vitamin A monograph & interactions

Spirulina

Interacts with
327 drugs
300 mg per serving Form: Arthrospira platensis

Blue-green algae are nutrient-rich aquatic microorganisms (such as spirulina and Klamath Lake algae) taken as a supplement for energy, nutrition, and...

Spirulina monograph & interactions

Calendula powder

Interacts with
248 drugs
50 mg per serving

Calendula is a flowering plant whose petals are used mainly in skin creams, oils, and ointments to soothe minor irritation and support wound healing....

Calendula powder monograph & interactions

Artichoke 4:1 extract

Interacts with
363 drugs
50 mg per serving

Artichoke leaf extract is a generally well-tolerated supplement that may have a mild cholesterol-lowering effect and is often used for indigestion, th...

Artichoke 4:1 extract monograph & interactions

Zinc

Interacts with
67 drugs
25 mg per serving Form: Zinc Alpha-Ketoglutarate, Zinc Citrate, Zinc Fumarate, Zinc Malate, Zinc Succinate

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

Copper

Interacts with
31 drugs
2 mg per serving Form: Copper Alpha-Ketoglutarate, Copper Citrate, Copper Fumarate, Copper Milate, Copper Succinate

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

Flavonoid extract

200 mg per serving

Other (inactive) ingredients: Gelatin, Silica, Dibasic Calcium Phosphate, Sucrose, Ethyl Cellulose, Hypromellose, Soybean Oil, Magnesium Stearate. These complete the product’s ingredient list but are not active constituents.

Interaction report

The Ultimate AntiOxidant Formula by Natrol Drug Interactions

Want to check YOUR meds against The Ultimate AntiOxidant Formula?

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
1,577Drugs
30 Major 1,447 Moderate 100 Minor

Ingredients driving the most interactions

Turmeric 1,133
Milk Thistle 954
Grape 910
Vitamin E 764
Niacin 727

Individual Drug Interactions

The ingredients in The Ultimate AntiOxidant Formula interact with 1,577 drugs. Click any drug to see the details.

17 of the 17 ingredients in The Ultimate AntiOxidant Formula interact with drugs. Each result below shows which ingredient is responsible. Turmeric Milk Thistle Grape Vitamin E Niacin Vitamin A Artichoke 4:1 extract Spirulina Selenium Bilberry Calendula powder Rose Hips Vitamin C Hawthorn Calcium Zinc Copper

Each ingredient & the kinds of drugs it affects

For each ingredient in The Ultimate AntiOxidant Formula 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.

Turmeric24 drug types · 1,133 drugs

Alkylating Agents

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression. However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

Likelihood Possible Evidence D
Amlodipine (Norvasc)

Taking turmeric with amlodipine may increase levels of amlodipine.
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone. Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro. Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk. It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes. Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction. Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo.

Likelihood Possible Evidence B
Antitumor Antibiotics

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65%. However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

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

Turmeric might increase or decrease levels of drugs metabolized by CYP3A4.
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4. Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib. In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition.
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. An animal model suggests that induction of CYP3A4 occurs after daily curcumin use for 1 week. However, the induction of CYP3A4 by turmeric has not been reported in humans.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs. Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

Likelihood Possible Evidence D
Sulfasalazine (Azulfidine)

Turmeric might increase the effects and adverse effects of sulfasalazine.
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Turmeric might increase the effects and adverse effects of tacrolimus.
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition. In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4.

Likelihood Possible Evidence D
Talinolol

Turmeric may reduce the absorption of talinolol in some situations.
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day. The clinical significance of this effect is unclear.

Likelihood Probable Evidence B
Tamoxifen (Nolvadex)

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers.

Likelihood Possible Evidence B
Topoisomerase I Inhibitors

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71%. However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have.

Likelihood Possible Evidence D
Tramadol (Ultram)

Theoretically, turmeric might increase or decrease levels of tramadol.
Animal research suggests that a single dose of curcumin, a constituent of turmeric, may increase tramadol's maximum concentration (Cmax) by inhibiting metabolism, while continued daily use for 7 days may reduce the area under the curve (AUC) due to the induction of drug-metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4). However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Turmeric might increase the risk of bleeding with warfarin.
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10. Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro, which may produce additive effects when taken with warfarin.

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

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2. However, other in vitro research suggests that curcumin does not significantly affect CYP1A2.

Likelihood Possible Evidence D
Docetaxel (Taxotere)

Theoretically, turmeric might increase blood levels of oral docetaxel.
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors.

Likelihood Possible Evidence D
Glyburide (Diabeta, Others)

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research.

Likelihood Possible Evidence B
Losartan (Cozaar)

Theoretically, turmeric might increase the effects of losartan.
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan.

Likelihood Possible Evidence D
Norfloxacin (Noroxin)

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity.

Likelihood Possible Evidence D
Paclitaxel (Abraxane, Onxol)

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant. Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Turmeric full monograph & interactions

Milk Thistle17 drug types · 954 drugs

Antidiabetes Drugs

Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs. Additionally, animal research shows that milk thistle extract increases the metformin maximum plasma concentration and area under the curve and decreases the renal clearance of metformin, due to inhibition of the multi-drug and toxin extrusion protein 1 (MATE1) renal tubular transport protein.

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

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.

Likelihood Possible Evidence D
Ledipasvir

Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.

Likelihood Possible Evidence D
Morphine

Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Animal research shows that milk thistle reduces serum levels of morphine by up to 66%. In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

Likelihood Possible Evidence D
Raloxifene (Evista)

Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Milk thistle might decrease the clearance of sirolimus.
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients. It is unclear if this interaction occurs in patients without hepatic impairment.

Likelihood Possible Evidence B
Sofosbuvir (Solvaldi)

Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion. Whether this interaction occurs in humans is not known.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, milk thistle might increase the effects of warfarin.
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement. Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin.

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

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.

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

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.

Likelihood Unlikely Evidence D
Estrogens

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.

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

Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin.

Likelihood Unlikely Evidence D
Indinavir (Crixivan)

Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25%. However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir. Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir.

Likelihood Unlikely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.

Likelihood Unlikely Evidence B
Milk Thistle full monograph & interactions

Grape9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

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

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

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

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

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

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

Likelihood Possible Evidence D
Midazolam (Versed)

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

Likelihood Possible Evidence D
Phenacetin

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

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

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

Likelihood Unlikely Evidence D
Grape full monograph & interactions

Vitamin E8 drug types · 764 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.
There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

Likelihood Possible Evidence B
Antitumor Antibiotics

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.
There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

A specific form of vitamin E might increase absorption and levels of cyclosporine.
There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients. However, this interaction is unlikely to occur with the usual forms of vitamin E.

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

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

Likelihood Possible Evidence D
Selumetinib (Koselugo)

Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.
Selumetinib contains 48-54 IU vitamin E per capsule. The increased risk of bleeding with vitamin E appears to be dose-dependent. Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Using vitamin E with warfarin might increase the risk of bleeding.
Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding,. At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin. Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations.

Likelihood Possible Evidence B
Niacin

Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people 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%. Vitamin E alone combined with a statin does not seem to decrease HDL levels. It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Vitamin E full monograph & interactions

Niacin15 drug types · 727 drugs

Alcohol (Ethanol)

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

Likelihood Probable Evidence D
Allopurinol (Zyloprim)

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

Likelihood Probable Evidence C
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antidiabetes Drugs

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

Likelihood Probable Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence B
Bile Acid Sequestrants

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

Likelihood Possible Evidence D
Gemfibrozil (Lopid)

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

Likelihood Possible Evidence D
Hepatotoxic Drugs

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

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

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

Likelihood Possible Evidence D
Probenecid (Benemid)

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

Likelihood Probable Evidence C
Sulfinpyrazone (Anturane)

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

Likelihood Probable Evidence C
Thyroid Hormone

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

Likelihood Probable Evidence D
Transdermal Nicotine (Nicoderm)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence D
Aspirin

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

Likelihood Likely Evidence B
Niacin full monograph & interactions

Vitamin A4 drug types · 387 drugs

Retinoids

Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.
Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements.

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.
The tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk of adverse effects. Doses of vitamin A above the UL can cause hepatotoxicity, ranging from elevated liver enzymes to liver failure.

Likelihood Possible Evidence C
Tetracycline Antibiotics

Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.
Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition. Avoid high doses of vitamin A in people taking tetracyclines chronically.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.
Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism. Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.

Likelihood Possible Evidence D
Vitamin A full monograph & interactions

Artichoke 4:1 extract4 drug types · 363 drugs

Antidiabetes Drugs

Theoretically, artichoke leaf extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
A meta-analysis of small clinical studies shows that taking artichoke leaf extract for 8-12 weeks can modestly reduce fasting plasma glucose when compared with placebo.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, artichoke leaf extract may increase the risk of hypotension when taken with antihypertensive drugs.
A meta-analysis of small clinical studies in patients with hypertension shows that taking artichoke can reduce systolic blood pressure by around 3 mmHg and diastolic blood pressure by around 2 mmHg when compared with placebo.

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

Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2B6.
In vitro research shows that artichoke leaf extract inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

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

Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2C19.
In vitro research shows that artichoke leaf extract inhibits CYP2C19 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Artichoke 4:1 extract full monograph & interactions

Spirulina3 drug types · 327 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, spirulina blue-green algae might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs. However, this is unlikely.
Spirulina blue-green algae have shown antiplatelet and anticoagulant effects in vitro. However, one preliminary study in 24 patients receiving spirulina blue-green algae 2.3 grams daily for 2 weeks showed no effect on platelet activation or measures of clotting time.

Likelihood Unlikely Evidence D
Antidiabetes Drugs

Theoretically, taking blue-green algae with antidiabetes drugs might increase the risk of hypoglycemia.
Human research shows that spirulina blue-green algae can have hypoglycemic effects in patients with diabetes, at least some of whom were using antidiabetes drugs. However, blue-green algae does not seem to improve glycated hemoglobin (HbA1c) levels in patients with diabetes. A meta-analysis of animal studies also suggests that spirulina blue-green algae have hypoglycemic effects.

Likelihood Possible Evidence B
Immunosuppressants

Theoretically, concurrent use of blue-green algae might interfere with immunosuppressive therapy.
Blue-green algae have been shown to stimulate the immune system.

Likelihood Possible Evidence D
Spirulina full monograph & interactions

Selenium6 drug types · 321 drugs

Anticoagulant/Antiplatelet Drugs

Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.

Likelihood Possible Evidence D
Barbiturates

Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.

Likelihood Possible Evidence D
Contraceptive Drugs

Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.

Likelihood Possible Evidence B
Niacin

Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) 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 selenium, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Selenium full monograph & interactions

Bilberry4 drug types · 275 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, bilberry fruit extract might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro, animal, and clinical research suggest that anthocyanidin extracts from bilberry can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, bilberry leaf or fruit extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research suggests that bilberry leaf extract might have blood glucose-lowering activity. Also, one small clinical trial in patients with type 2 diabetes shows that taking bilberry fruit extract 470 mg as a single dose prior to an oral glucose tolerance test lowers plasma glucose levels when compared with placebo.

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

Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.
Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity. This effect has not been reported in humans.

Likelihood Possible Evidence D
Erlotinib (Tarceva)

Theoretically, bilberry fruit extract might reduce the efficacy of erlotinib.
In vitro research suggests that bilberry fruit extract and its constituents, delphinidin and delphinidin-3-O-glucoside, inhibit the activity of erlotinib. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Bilberry full monograph & interactions

Calendula powder1 drug type · 248 drugs

Cns Depressants

Theoretically, calendula might have additive effects when used with CNS depressants, although this appears to be unlikely.
Although some animal research has suggested that a saponoside constituent in calendula may have sedative effects, calendula has been used for over 30 years without reports of sedation in humans.

Likelihood Unlikely Evidence D
Calendula powder full monograph & interactions

Rose Hips8 drug types · 213 drugs

Alkylating Agents

Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of alkylating agents but might also reduce the oxidative damage caused by certain alkylating agents.
Rose hip contains vitamin C. 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. Further, some animal research suggests that the antioxidant effects of rose hip might attenuate cyclophosphamide-induced testicular toxicity. More evidence is needed to determine what effect, if any, antioxidants found in rose hip, such as vitamin C, have on the effectiveness and adverse effects of chemotherapy.

Likelihood Possible Evidence D
Aluminum

Theoretically, rose hip might increase the amount of aluminum absorbed from aluminum compounds.
Rose hip contains vitamin C. Theoretically, vitamin C increases the absorption of aluminum. Concomitant use might increase aluminum absorption, but the clinical significance of this is unknown. Administer rose hip two hours before or four hours after antacids.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, rose hip might reduce the effectiveness of anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that a constituent of rose hip, rugosin E, can induce platelet aggregation. This has not been shown in humans. Theoretically, concomitant use of rose hip might reduce the effectiveness of antiplatelet or anticoagulant drugs.

Likelihood Possible Evidence D
Antitumor Antibiotics

Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of antitumor antibiotics.
Rose hip contains the antioxidant vitamin C. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as antitumor antibiotics. In contrast, other researchers theorize that antioxidants might make antitumor antibiotic 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 antitumor antibiotic chemotherapy.

Likelihood Possible Evidence D
Estrogens

Theoretically, rose hip might increase blood levels of estrogens.
Rose hip contains vitamin C. Increases in plasma estrogen levels of up to 55% have occured 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. However, increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements.

Likelihood Possible Evidence D
Lithium

Theoretically, rose hip might increase blood levels of lithium.
Rose hip is thought to have diuretic properties. Theoretically, due to these potential diuretic effects, rose hip might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

Likelihood Probable Evidence D
Aspirin

Theoretically, rose hip might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Rose hip contains vitamin C. It has been suggested that acidification of the urine by vitamin C can decrease the urinary excretion of salicylates, increasing 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. The vitamin C content of rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and aspirin is unlikely.

Likelihood Unlikely Evidence B
Warfarin (Coumadin)

Theoretically, rose hip might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Rose hip contains vitamin C. High doses of vitamin C may reduce the response to warfarin, possibly by causing diarrhea and reducing warfarin absorption. This occurred in two people who took up to 16 grams daily of vitamin C, and resulted in decreased prothrombin time. Lower doses of 5-10 grams daily of vitamin C can also reduce warfarin absorption, but this does not seem to be clinically significant. The vitamin C content of rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and warfarin is unlikely.

Likelihood Unlikely Evidence D
Rose Hips 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

Hawthorn6 drug types · 191 drugs

Nitrates

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

Likelihood Probable Evidence D
Phosphodiesterase-5 Inhibitors

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Beta-Blockers

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

Likelihood Possible Evidence D
Calcium Channel Blockers

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

Likelihood Possible Evidence D
Digoxin (Lanoxin)

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

Likelihood Possible Evidence D
Hawthorn full monograph & interactions

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

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

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

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

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

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

Likelihood Probable Evidence B
Aluminum

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

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

Likelihood Possible Evidence B
Digoxin (Lanoxin)

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

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

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

Likelihood Probable Evidence B
Lithium

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

Likelihood Possible Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Raltegravir (Isentress)

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

Likelihood Possible Evidence B
Sotalol (Betapace)

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

Likelihood Possible Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence C
Thiazide Diuretics

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

Likelihood Probable Evidence C
Verapamil (Calan, Others)

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

Likelihood Probable Evidence D
Calcium Channel Blockers

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

Likelihood Unlikely Evidence D
Calcium full monograph & interactions

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

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
The maker

Brand information

Manufacturer and brand details for The Ultimate AntiOxidant Formula, from the product label.

Natrol

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Name
Natrol
Pharmacist Counseling Corner

The Ultimate AntiOxidant Formula by Natrol: Common Questions

Does The Ultimate AntiOxidant Formula by Natrol interact with any medications?
Yes. Based on its ingredients, The Ultimate AntiOxidant Formula has a known interaction with 1,577 medications, including 30 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
The Ultimate AntiOxidant Formula 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.
Does this supplement have any fillers?
Yes, it has inactive ingredients: gelatin capsule, silica, dibasic calcium phosphate, sucrose, ethyl cellulose, hypromellose, soybean oil, and magnesium stearate.
Can I take this while pregnant?
Several ingredients lack sufficient safety data for pregnancy. Calcium and vitamin C at recommended levels are considered safe in pregnancy, but niacin, vitamin A (especially at high doses), milk thistle, turmeric, hawthorn, spirulina, calendula, and artichoke all have pregnancy cautions. Talk with your doctor or pharmacist about whether this product is right for you during pregnancy.
Is this safe while breastfeeding?
Calcium and vitamin C are considered safe at recommended amounts during breastfeeding. However, vitamin E, selenium, niacin, milk thistle, hawthorn, spirulina, and artichoke all have limited or insufficient breastfeeding safety data. Check with your doctor or pharmacist before taking it.
What is turmeric used for in this formula?
Turmeric is an antioxidant herb possibly effective for depression and high cholesterol, though evidence is limited. It's included as part of the product's overall antioxidant blend.
Can I take this if I have kidney disease?
Calcium can accumulate in kidneys at high doses, and vitamin C very high doses may cause kidney damage. Selenium excess can also stress the kidneys. If you have kidney disease, ask your pharmacist or doctor before starting, as the doses in this product and your individual kidney function matter.
Will this help prevent heart disease?
The evidence for antioxidant supplements in preventing heart disease is mixed and not established for most ingredients in this formula. Talk with your doctor about whether an antioxidant supplement is right for your individual risk factors.

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

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

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Go deeper

The Full Monographs Behind The Ultimate AntiOxidant Formula’s Ingredients

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

Herb & supplement monograph

Calcium

Interacts with 168 drugs

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

Read the full Calcium monograph → Herb & supplement monograph

Niacin

Interacts with 727 drugs

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

Read the full Niacin monograph → Herb & supplement monograph

Vitamin E

Interacts with 764 drugs

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitam...

Read the full Vitamin E 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

Selenium

Interacts with 321 drugs

Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...

Read the full Selenium monograph → Herb & supplement monograph

Vitamin A

Interacts with 387 drugs

Vitamin A is an essential nutrient important for vision, skin, immune function, and growth. Most people get enough from a balanced diet, and supplements are mainly useful for correcting a tr...

Read the full Vitamin A monograph → Herb & supplement monograph

Blue-green Algae

Interacts with 327 drugs

Blue-green algae are nutrient-rich aquatic microorganisms (such as spirulina and Klamath Lake algae) taken as a supplement for energy, nutrition, and general wellness. Evidence for most heal...

Read the full Blue-green Algae monograph → Herb & supplement monograph

Calendula

Interacts with 248 drugs

Calendula is a flowering plant whose petals are used mainly in skin creams, oils, and ointments to soothe minor irritation and support wound healing. Some early research is promising for ski...

Read the full Calendula monograph → Herb & supplement monograph

Artichoke

Interacts with 363 drugs

Artichoke leaf extract is a generally well-tolerated supplement that may have a mild cholesterol-lowering effect and is often used for indigestion, though the evidence is modest. It is not a...

Read the full Artichoke 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

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

Milk Thistle

Interacts with 954 drugs

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, th...

Read the full Milk Thistle monograph → Herb & supplement monograph

Rose Hip

Interacts with 213 drugs

Rose hip is the vitamin C–rich fruit of the wild rose, used traditionally for colds and joint pain. A standardized rose hip powder has some research support for easing osteoarthritis symptom...

Read the full Rose Hip monograph → Herb & supplement monograph

Turmeric

Interacts with 1,133 drugs

Turmeric is a popular spice whose main active compounds, curcuminoids, are studied mostly for inflammation and joint pain. Some research is promising, but quality is mixed and curcumin is po...

Read the full Turmeric monograph → Herb & supplement monograph

Hawthorn

Interacts with 191 drugs

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

Read the full Hawthorn monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

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

Read the full Grape monograph → Herb & supplement monograph

Bilberry

Interacts with 275 drugs

Bilberry is a blueberry-like fruit rich in antioxidant plant compounds called anthocyanins, and it has a long history of traditional use for eye health, circulation, and mild diarrhea. While...

Read the full Bilberry monograph →
Sources

Sources & How We Checked

The Ultimate AntiOxidant Formula'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 724 references behind this product’s interaction data

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

Calcium 62 references
  1. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
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Selenium 36 references
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Milk Thistle 69 references
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Hawthorn 25 references
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Grape 34 references
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Copper 11 references
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See these in context on the Copper monograph →

Bilberry 14 references
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See these in context on the Bilberry monograph →

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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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