Major interaction on record — check this product against your medications before combining. Based on 22 of 32 ingredients. Check your meds →
Dietary supplement

GI Natural Total Digestive Wellness Ingredients & Drug Interactions

by NaturesPlus

GI Natural Total Digestive Wellness label
See full label image
Tablet Or Pill 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 GI Natural Total Digestive Wellness 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

GI Natural Total Digestive Wellness is a dietary supplement by NaturesPlus with 32 active ingredients. Its ingredients are commonly taken for muscle recovery and sports performance, gut health and 'leaky gut', recovery from severe illness or injury.Based on those ingredients, 2,273 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Indian Cluster Bean extract, Beet, Vitamin E. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against GI Natural Total Digestive Wellness by NaturesPlus

Ask about any prescription or over-the-counter medication and we check it for interactions with GI Natural Total Digestive Wellness by NaturesPlus — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of GI Natural Total Digestive Wellness by NaturesPlus

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

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 6 of its 32 active ingredients.
  • “Enzyme-Rich Whole Food Blend” is a proprietary blend — the label gives one combined amount (25 mg) without saying how much of each component you get.
  • “Short-Chain Fatty-Acid–Promoting Prebiotic Blend” is a proprietary blend — the label gives one combined amount (400 mg) without saying how much of each component you get.
  • “Live Enzyme Blend” is a proprietary blend — the label gives one combined amount (25 mg) without saying how much of each component you get.

GI Natural Total Digestive Wellness contains 32 active ingredients, primarily digestive enzymes and supporting nutrients. The enzyme blend includes L-glutamine, protease, lipase, amylase, cellulase, xylanase, pectinase, and hemicellulase — all designed to help break down and absorb different types of food.

Bromelain (from pineapple) and papain (from papaya) are proteases that further aid protein digestion. The product also includes the probiotic Bifidobacterium breve, which supports healthy gut bacteria, plus mineral and vitamin support from calcium, zinc, and selenium.

Additional ingredients are fruit extracts (apple pectin, beet, papaya, banana, mango) and the prebiotic fructooligosaccharides, along with lactase for those with lactose sensitivity. Inactive ingredients include microcrystalline cellulose, dicalcium phosphate, and plant-based binders.

Does it work?

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

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

Why this rating?
  • The label markets this product for: support for healthy GI mucosal lining.
  • We looked for evidence on: Antibiotic-associated diarrhea, Antiretroviral-associated diarrhea, Intestinal permeability, Leaky gut syndrome, GI inflammation.
  • The strongest evidence on file: Lactobacillus Acidophilus is rated "Possibly Effective" for Antibiotic-associated diarrhea (Natural Medicines).
  • Also on file: Banana is rated "Possibly Effective" for Diarrhea.
  • Also on file: Pectin is rated "Insufficient Reliable Evidence To Rate" for Diarrhea.

The evidence for effectiveness varies widely across this product's ingredients. Calcium is effective for kidney failure and dyspepsia, and likely effective for osteoporosis.

L-glutamine is effective for sickle cell disease and possibly effective for HIV-related wasting and recovery from surgery or critical illness. Vitamin C is effective for vitamin C deficiency and possibly effective for anemia and exercise-related infections.

Selenium is likely effective for selenium deficiency and possibly effective for autoimmune thyroid disease. Vitamin E is effective for vitamin E deficiency and possibly effective for Alzheimer disease.

Zinc is effective for zinc deficiency and possibly effective for acne and age-related macular degeneration. Lactase is effective for lactose intolerance.

However, for many ingredients in this formula — papain, bromelain, lipase, protease, fructooligosaccharides, Bifidobacterium breve, and the fruit extracts — the evidence is insufficient to establish effectiveness for any condition, meaning we simply don't have enough data to say whether they work.

The evidence, ingredient by ingredient Glutamine Calcium Vitamin C Selenium Vitamin E Zinc Beet Papaya

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 22 of the 22 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 22 of 22.
  • General safety write-ups exist for 22 of 22.
  • 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, vitamin C, vitamin E, selenium, and zinc are safe at normal amounts but can cause problems at high doses.

Glutamine is generally well tolerated in healthy adults but should be used only under medical supervision by people with kidney or liver disease; it's not recommended in supplement doses during pregnancy or breastfeeding. Papain and bromelain are generally well tolerated short-term, but papain should be avoided in pregnancy.

Bromelain safety during pregnancy and breastfeeding is unknown and best avoided. Protease and lipase are generally well tolerated but have limited long-term safety data.

Bifidobacterium breve is well tolerated in healthy people but should be used cautiously in very ill or immunocompromised individuals. Common mild side effects from various ingredients include gastrointestinal upset (bloating, gas, diarrhea, constipation, nausea), which are dose-dependent and often improve with lower doses.

Side effects, ingredient by ingredient Glutamine Calcium Vitamin C Selenium Vitamin E Zinc Beet Papaya

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 22 matched ingredients can interact with medications — Papain, Beet, Papaya, Pectin, Calcium, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 2,274 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check with your pharmacist if you're on HIV integrase inhibitors (dolutegravir, elvitegravir, or raltegravir) — Major interactions with calcium require careful spacing of doses. Also check if you take the antibiotic ceftriaxone intravenously (Major risk of dangerous precipitation).

Blood thinners like warfarin, anticoagulants, and antiplatelet drugs (aspirin, clopidogrel) warrant review because of Moderate interactions with vitamin E, selenium, papain, and bromelain. Thyroid medication (levothyroxine), quinolone and tetracycline antibiotics, and HIV protease inhibitors should all be reviewed before you start, as calcium, zinc, and other ingredients carry Moderate interactions that may affect drug levels.

Check your own medication Run your meds through the checker above

The bottom line

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

This broad-spectrum digestive enzyme and probiotic formula may help people with general digestive issues, though evidence is strongest for the individual nutrients like calcium and zinc rather than the enzyme blend as a whole. If you take any prescription medications — especially blood thinners, HIV drugs, antibiotics, thyroid medication, heart medications, or cancer treatments — you need to check your exact drugs against the interaction tool on this page before starting.

Talk to your pharmacist about timing and whether this product is right for you alongside your current regimen.

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

Assessment coverage: 22 of 32 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 27, 2021.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about GI Natural Total Digestive Wellness, straight from the product label.

Brand NaturesPlus
Barcode (UPC) 097467043862
Net contents 90 Bi-Layered Tablet(s)
Market status On market
Date entered into DSLD Jul 27, 2021
DSLD ID 249677
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for GI Natural Total Digestive Wellness by NaturesPlus, 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:
3 Bi-Layered Tablet(s)
Maximum serving Sizes:
3 Bi-Layered Tablet(s)
Servings per container
30
UPC/BARCODE
097467043862
IngredientAmount% DV
L-Glutamine1000 mg--
Calcium300 mg23%
Vitamin C200 mg222%
Selenium35 mcg64%
Amylase0 NP--
Papain0 NP--
Bromelain0 NP--
Vitamin E67 mg447%
Protease0 NP--
Lipase0 NP--
Zinc15 mg136%
Lactase0 NP--
Fructooligosaccharides0 NP--
Cellulase0 NP--
Bifidobacterium breve0 NP--
Xylanase0 NP--
Pectinase0 NP--
Pineapple0 NP--
Hemicellulase0 NP--
Apple Pectin0 NP--
Oxidase0 NP--
Beet0 NP--
Mango0 NP--
Papaya0 NP--
Banana0 NP--
Raspberry0 NP--
Cherry0 NP--
Arabinogalactans0 NP--
Date0 NP--
Enzyme-Rich Whole Food Blend25 mg--
Lactospore0 NP--
Indian Cluster Bean extract0 NP--
Short-Chain Fatty-Acid–Promoting Prebiotic Blend400 mg--
Lactobacillus acidophilus0 NP--
Live Enzyme Blend25 mg--
Proprietary Probiotic Blend25 mg--

Other ingredients: Microcrystalline Cellulose, Di-Calcium Phosphate, Hydroxypropyl Methylcellulose, Stearic Acid, Magnesium Stearate, Silica, Vegetable Cellulose, Beet Juice, Tapioca Maltodextrin, organic Sunflower Lecithin, organic Palm Oil, organic Guar Gum

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.
Formulation

Nutritional support for a healthy GI mucosal lining

Optimal digestive health and overall wellness depend on a healthy gut, and GI Natural Total Digestive Wellness not only helps heal the GI tract’s vital mucosal lining but strengthens and vitalizes this tissue. Uniquely formulated as a bi-layered tablet, the fast-release layer optimizes digestive comfort and energy, while the slow-release layer cleanses and rejuvenates. Feel the soothing natural comfort of a healthy digestive tract with the power of GI Natural Total Digestive Wellness!

Free from artificial colors and preservatives. Free from yeast, milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans.

Vegetarian

Gluten Free

Formula

GI Natural Total Digestive Wellness by Nature’s Plus is a clinically designed formulation of high-potency L-Glutamine complexed with synergistic and supportive nutrients for a healthy GI mucosal tract.

L-Glutamine Enzymes Probiotics Whole Foods Essential Cofactors

Storage

Keep tightly closed in a cool, dry place.

Precautions

Keep out of reach of children.

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.

Brand IP Statement(s)

Lactospore is a registered trademark of Sabinsa Corp. Natural Organics

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Directions: Take 3 tablets daily, or as directed by your healthcare professional.

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

See for yourself

GI Natural Total Digestive Wellness by NaturesPlus label

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

GI Natural Total Digestive Wellness 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 GI Natural Total Digestive Wellness by NaturesPlus

These are the 32 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Bi-Layered Tablet(s) Dosage formTablet Or Pill 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.

L-Glutamine

Interacts with
50 drugs
1000 mg per serving

Glutamine is the most abundant amino acid in the body and is usually made in your muscles. A prescription form is FDA-approved to help reduce sickle c...

L-Glutamine monograph & interactions

Calcium

Interacts with
168 drugs
300 mg per serving Form: Calcium Carbonate, Calcium Phosphate

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

Calcium monograph & interactions

Vitamin C

Interacts with
207 drugs
200 mg per serving Form: Ascorbic Acid

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

Vitamin C monograph & interactions

Selenium

Interacts with
321 drugs
35 mcg per serving Form: 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 E

Interacts with
764 drugs
67 mg 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

Zinc

Interacts with
67 drugs
15 mg per serving Form: Zinc Gluconate

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

Enzyme-Rich Whole Food Blend

25 mg per serving

Short-Chain Fatty-Acid–Promoting Prebiotic Blend

400 mg per serving

Live Enzyme Blend

25 mg per serving

Proprietary Probiotic Blend

25 mg per serving

Other (inactive) ingredients: Microcrystalline Cellulose, Di-Calcium Phosphate, Hydroxypropyl Methylcellulose, Stearic Acid, Magnesium Stearate, Silica, Vegetable Cellulose, Beet Juice, Tapioca Maltodextrin, Organic Sunflower Lecithin, Organic Palm Oil, Organic Guar Gum. These complete the product’s ingredient list but are not active constituents.

Interaction report

GI Natural Total Digestive Wellness by NaturesPlus Drug Interactions

Want to check YOUR meds against GI Natural Total Digestive Wellness?

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
2,273Drugs
7 Major 2,260 Moderate 6 Minor

Ingredients driving the most interactions

Indian Cluster Bean extract 2,025
Beet 861
Vitamin E 764
Selenium 321
Vitamin C 207

Individual Drug Interactions

The ingredients in GI Natural Total Digestive Wellness interact with 2,273 drugs. Click any drug to see the details.

17 of the 32 ingredients in GI Natural Total Digestive Wellness interact with drugs. Each result below shows which ingredient is responsible. Indian Cluster Bean extract Beet Vitamin E Selenium Vitamin C Bifidobacterium breve Lactospore Lactobacillus acidophilus Calcium Bromelain Arabinogalactans Papaya Zinc L-Glutamine Apple Pectin Banana Papain

Each ingredient & the kinds of drugs it affects

For each ingredient in GI Natural Total Digestive Wellness 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.

Indian Cluster Bean extract5 drug types · 2,025 drugs

Ethinyl Estradiol

Theoretically, guar gum might reduce the absorption of ethinyl estradiol, potentially decreasing its effectiveness.
Animal research shows that taking guar gum with ethinyl estradiol decreases ethinyl estradiol absorption. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Metformin (Glucophage)

Guar gum might reduce the absorption of metformin, potentially decreasing its effectiveness.
A small study in healthy volunteers shows that guar gum reduces the absorption rate of metformin.

Likelihood Probable Evidence B
Oral Drugs

Guar gum might reduce the absorption of some oral drugs, potentially decreasing their effectiveness.
Clinical research shows that guar gum reduces or slows absorption of medications such as penicillin and metformin. To avoid changes in absorption, take guar gum 30-60 minutes after oral medications.

Likelihood Possible Evidence B
Penicillin

Guar gum might reduce the absorption of penicillin, potentially decreasing its effectiveness.
A small clinical study in healthy volunteers shows that taking guar gum with penicillin results in decreased penicillin absorption and reduced penicillin levels.

Likelihood Probable Evidence B
Digoxin (Lanoxin)

Guar gum might slow digoxin absorption, but it does not seem to impact how much digoxin is absorbed overall.
Two small studies in healthy volunteers show no change in the overall extent of digoxin absorption, although early absorption was slowed, when taken with guar gum.

Likelihood Possible Evidence B
Indian Cluster Bean extract full monograph & interactions

Beet3 drug types · 861 drugs

Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, beet might increase the levels of CYP3A4 substrates.
In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole.

Likelihood Possible Evidence D
Antihypertensive Drugs

Beet and beetroot contain nitrates, which can cause vasodilation, potentially leading to lower blood pressure. However, a study published in the European Journal of Clinical Nutrition using concentrated beetroot juice found no significant impact on blood pressure or heart rate in different age groups. Other small clinical studies suggest that while beet consumption might transiently lower blood pressure due to vessel dilation, there's no consistent evidence of a lasting effect. Overall, the theoretical risk of reduced blood pressure due to beet's nitrate content exists, but studies generally indicate a low and temporary impact rather than a sustained decrease.

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

Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research suggests that beet induces CYP1A2 enzymes.

Likelihood Possible Evidence D
Beet 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

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

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

Bifidobacterium breve1 drug type · 182 drugs

Antibiotic Drugs

Theoretically, taking Bifidobacterium breve with antibiotic drugs might decrease the effectiveness of B. breve.
Since B. breve preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. breve preparations by at least 2 hours.

Likelihood Probable Evidence D
Bifidobacterium breve full monograph & interactions

Lactospore1 drug type · 182 drugs

Antibiotic Drugs

Theoretically, taking antibiotics with Bacillus coagulans might decrease the effectiveness of B. coagulans.
B. coagulans preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. coagulans preparations by at least two hours.

Likelihood Probable Evidence D
Lactospore full monograph & interactions

Lactobacillus acidophilus1 drug type · 182 drugs

Antibiotic Drugs

Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.
L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.

Likelihood Probable Evidence D
Lactobacillus acidophilus 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

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Likelihood Possible Evidence B
Bromelain full monograph & interactions

Arabinogalactans1 drug type · 121 drugs

Immunosuppressants

Theoretically, larch arabinogalactan might interfere with immunosuppression therapy due to immunostimulant effects. Immunosuppressant drugs include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and other drugs.

Likelihood Possible Evidence D
Arabinogalactans full monograph & interactions

Papaya4 drug types · 92 drugs

Amiodarone (Cordarone)

Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70%. This interaction has not been reported in humans.

Likelihood Probable Evidence D
Antidiabetes Drugs

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D
Papaya 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

L-Glutamine1 drug type · 50 drugs

Anticonvulsants

Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
Glutamine is metabolized to the excitatory neurotransmitter glutamate. Glutamate might have antagonistic effects with anticonvulsant drugs. However, this interaction has not yet been reported in humans.

Likelihood Possible Evidence D
L-Glutamine full monograph & interactions

Apple Pectin3 drug types · 23 drugs

Digoxin (Lanoxin)

Theoretically, pectin might reduce the absorption of digoxin, potentially decreasing its effectiveness.
A small clinical study shows that taking digoxin with a kaolin-pectin suspension reduces the absorption of digoxin by about 62%. It is unclear if these effects are due to pectin, kaolin, or the combination.

Likelihood Possible Evidence B
Lovastatin (Mevacor)

Theoretically, pectin might reduce the absorption of lovastatin, potentially decreasing its effectiveness.
Case reports suggest that concomitant use of pectin and lovastatin might reduce the cholesterol-lowering effect of lovastatin, possibly due to reduced intestinal absorption of lovastatin.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, pectin might reduce the absorption of tetracycline antibiotics, potentially decreasing their effectiveness.
A small clinical study shows that taking tetracycline with bismuth subsalicylate in a kaolin-pectin suspension reduces the absorption of tetracycline by about 34%. It is unclear if these effects are due to pectin, kaolin, bismuth subsalicylate, or the combination.

Likelihood Possible Evidence B
Apple Pectin full monograph & interactions

Banana1 drug type · 5 drugs

Levodopa

Taking banana may reduce the effectiveness of levodopa.
A case report describes apparent wearing off in a patient with Parkinson disease after eating a banana every day. The wearing off subsided after removing dietary bananas.

Likelihood Possible Evidence D
Banana full monograph & interactions

Papain1 drug type · 2 drugs

Warfarin (Coumadin)

Theoretically, papain might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D
Papain full monograph & interactions
The maker

Brand information

Manufacturer and brand details for GI Natural Total Digestive Wellness, from the product label.

NaturesPlus

See all NaturesPlus products
Name
Natural Organics Laboratories, Inc. makers of Nature's Plus
Street Address
9500 New Horizons Blvd
City
Amityville
State
New York
ZipCode
11701
Web Address
www.naturesplus.com
Pharmacist Counseling Corner

GI Natural Total Digestive Wellness by NaturesPlus: Common Questions

Does GI Natural Total Digestive Wellness by NaturesPlus interact with any medications?
Yes. Based on its ingredients, GI Natural Total Digestive Wellness has a known interaction with 2,273 medications, including 7 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
GI Natural Total Digestive Wellness contains 32 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is this product safe to take if I'm pregnant or breastfeeding?
It depends on the individual ingredient. Calcium, vitamin C, vitamin E, lactase, and banana are considered likely or possibly safe in pregnancy, but L-glutamine, papain, and bromelain are not recommended in supplement doses during pregnancy. For breastfeeding, calcium, vitamin E, lactase, and banana are generally acceptable, but L-glutamine, papain, bromelain, and protease lack enough safety data — check with your doctor or pharmacist for personalized guidance.
Can this help with digestive problems like bloating or constipation?
The enzymes in this product are designed to support digestion, but the evidence is strongest for individual nutrients like calcium (which is effective for dyspepsia) rather than the enzyme blend itself. Digestive enzymes have insufficient evidence to confirm they work for most conditions. Talk to your pharmacist about whether this formulation fits your specific digestive concern.
What are the most common side effects?
Mild gastrointestinal upset is most common — bloating, gas, diarrhea, constipation, or nausea — especially with calcium, glutamine, and the enzyme and prebiotic ingredients. These effects are usually dose-dependent and often improve if you take less. If they persist or worsen, stop and contact your pharmacist.
Does this contain any animal products?
The product contains several plant-derived enzymes (bromelain from pineapple, papain from papaya) and a probiotic (Bifidobacterium breve). Some inactive ingredients like di-calcium phosphate may be derived from animal sources depending on the manufacturer's sourcing — check the label or contact the company directly if this matters to you.
Can I take this with my other supplements?
This product's interactions are primarily with prescription medications rather than other supplements. However, if you're taking high-dose vitamin E or selenium elsewhere, be aware this formula adds to your total dose. And if you're taking zinc from another source, combined intake may exceed safe limits. List all your supplements when you check interactions with your medications.
What makes this 'total' wellness compared to a basic enzyme formula?
This product combines digestive enzymes (protease, lipase, amylase, and others), probiotics (Bifidobacterium breve), micronutrients (calcium, zinc, vitamin C, vitamin E, selenium), and fruit extracts. The idea is to address enzyme support, gut bacteria, nutrient absorption, and overall digestive health in one tablet. However, evidence for the enzyme and probiotic portions is insufficient, so the strongest support comes from the individual nutrients.

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.

GI Natural Total Digestive Wellness label
Go deeper

The Full Monographs Behind GI Natural Total Digestive Wellness’s Ingredients

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

Herb & supplement monograph

Glutamine

Interacts with 50 drugs

Glutamine is the most abundant amino acid in the body and is usually made in your muscles. A prescription form is FDA-approved to help reduce sickle cell disease complications, but for most...

Read the full Glutamine monograph → Herb & supplement monograph

Calcium

Interacts with 168 drugs

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

Read the full Calcium monograph → Herb & supplement monograph

Vitamin 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 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

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

Beet

Interacts with 861 drugs

Beet, especially beetroot juice, is a nitrate-rich food that may modestly lower blood pressure and slightly improve exercise performance in some people. It is generally safe as a food, but s...

Read the full Beet monograph → Herb & supplement monograph

Papaya

Interacts with 92 drugs

Papaya is a tropical fruit that is nutritious and generally safe to eat as food, and it contains an enzyme called papain used as a digestive aid and meat tenderizer. Papaya leaf extract is b...

Read the full Papaya monograph → Herb & supplement monograph

Banana

Interacts with 5 drugs

Bananas are a nutritious, widely eaten fruit that provide potassium, fiber, vitamin B6, and quick energy, and they are part of a healthy diet. While some traditional uses (like easing diarrh...

Read the full Banana monograph → Herb & supplement monograph

Date Palm

Date palm fruit is a nutritious food rich in natural sugars, fiber, and antioxidants, and is widely eaten as part of a healthy diet. Beyond its value as food, evidence for medicinal benefits...

Read the full Date Palm monograph → Herb & supplement monograph

Pectin

Interacts with 23 drugs

Pectin is a natural soluble fiber found in fruits like apples and citrus, and it is widely used in foods and as a fiber supplement. It may modestly help with cholesterol, blood sugar, and di...

Read the full Pectin monograph → Herb & supplement monograph

Larch Arabinogalactan

Interacts with 121 drugs

Larch arabinogalactan is a soluble fiber from larch trees that is mainly used as a prebiotic and for immune support. Early research is interesting but limited, and most claims are not yet fi...

Read the full Larch Arabinogalactan monograph → Herb & supplement monograph

Guar Gum

Interacts with 2,025 drugs

Guar gum is a soluble, gel-forming fiber from the guar bean that may modestly help with cholesterol, blood sugar, and bowel regularity. It is generally safe in food amounts, but concentrated...

Read the full Guar Gum monograph → Herb & supplement monograph

Papain

Interacts with 2 drugs

Papain is a protein-digesting enzyme from the papaya plant that is used in digestive supplements and some topical products. While it has clear food and laboratory uses, strong human evidence...

Read the full Papain monograph → Herb & supplement monograph

Bromelain

Interacts with 141 drugs

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early studies are promising, but the overall evi...

Read the full Bromelain monograph → Herb & supplement monograph

Proteolytic Enzymes (proteases)

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), trypsin, chymotrypsin, and pancreatin. Peo...

Read the full Proteolytic Enzymes (proteases) monograph → Herb & supplement monograph

Lipase

Lipase is a digestive enzyme that helps your body break down dietary fats. It is well established as part of prescription pancreatic enzyme therapy for people who cannot make enough of their...

Read the full Lipase monograph → Herb & supplement monograph

Lactase

Lactase is a digestive enzyme supplement that helps people who lack enough natural lactase break down lactose, the sugar in milk and dairy. It can reduce gas, bloating, cramping, and diarrhe...

Read the full Lactase monograph → Herb & supplement monograph

Fructo-oligosaccharides (fos)

Fructo-oligosaccharides (FOS) are a type of soluble fiber that acts as a prebiotic, meaning they feed the helpful bacteria in your gut. They are generally considered safe for most people in...

Read the full Fructo-oligosaccharides (fos) monograph → Herb & supplement monograph

Bifidobacterium Breve

Interacts with 182 drugs

Bifidobacterium breve is a 'friendly' gut bacterium taken as a probiotic, most often to support digestion and balance the gut microbiome. Some studies suggest possible benefits for certain d...

Read the full Bifidobacterium Breve monograph → Herb & supplement monograph

Bacillus Coagulans

Interacts with 182 drugs

Bacillus coagulans is a spore-forming probiotic that survives stomach acid well and may help with some digestive problems such as IBS, constipation, and certain types of diarrhea. The eviden...

Read the full Bacillus Coagulans monograph → Herb & supplement monograph

Lactobacillus Acidophilus

Interacts with 182 drugs

Lactobacillus acidophilus is a 'friendly' bacterium used as a probiotic to support gut and vaginal health. It is generally well tolerated in healthy people, and there is reasonable evidence...

Read the full Lactobacillus Acidophilus monograph →
Sources

Sources & How We Checked

GI Natural Total Digestive Wellness'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 490 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.

Glutamine 11 references
  1. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev 1999;4:239-48..
  2. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 1997;13:748-51.. PubMed
  3. Mebane AH. L-Glutamine and mania. Am J Psychiatry 984;141:1302-3.
  4. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000;130:1007S-15S.. PubMed
  5. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001;131:2556S-61S.. PubMed
  6. Chapman AG. Glutamate and epilepsy. J Nutr 2000;130:1043S-5S.. PubMed
  7. Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 2001;131:2578S-84S.. PubMed
  8. Laviano A, Molfino A, Lacaria MT, Canelli A, De Leo S, Preziosa I, Rossi Fanelli F. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study. Eur J Clin Nutr. 2014 Nov;68(11):1264-6. PubMed
  9. Endari (l-glutamine) [package insert]. Torrance, CA: Emmaus Medical,Inc; 2017.
  10. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med 2018;379(3):226-35. doi: 10.1056/NEJMoa1715971.
  11. Ogden HB, Child RB, Fallowfield JL, et al. Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study. Nutrients. 2020;12(10):2953. PubMed

See these in context on the Glutamine monograph →

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

See these in context on the Calcium monograph →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
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  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
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See these in context on the Vitamin C monograph →

Selenium 36 references
  1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  2. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
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  5. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
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Lipase 1 reference
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Banana 11 references
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Larch Arabinogalactan 8 references
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Date Palm 9 references
  1. Kwaasi, A. A., Harfi, H. A., Parhar, R. S., Saleh, S., Collison, K. S., Panzani, R. C., Al Sedairy, S. T., and Al Mohanna, F. A. Cross-reactivities between date palm (Phoenix dactylifera L.) polypeptides and foods implicated in the oral allergy syndrome.
  2. Bener, A., Safa, W., Abdulhalik, S., and Lestringant, G. G. An analysis of skin prick test reactions in asthmatics in a hot climate and desert environment. Allerg.Immunol.(Paris) 2002;34(8):281-286.
  3. Bauza, E., Dal Farra, C., Berghi, A., Oberto, G., Peyronel, D., and Domloge, N. Date palm kernel extract exhibits antiaging properties and significantly reduces skin wrinkles. Int.J.Tissue React. 2002;24(4):131-136.
  4. Blanco, C., Carrillo, T., Quiralte, J., Pascual, C., Martin, Esteban M., and Castillo, R. Occupational rhinoconjunctivitis and bronchial asthma due to Phoenix canariensis pollen allergy. Allergy 1995;50(3):277-280.
  5. Elkerm Y, Tawashi R. Date palm pollen as a preventative intervention in radiation- and chemotherapy-induced oral mucositis: a pilot study. Integr Cancer Ther. 2014;13(6):468-72. PubMed
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  7. Bagherzadeh Karimi A, Elmi A, Mirghafourvand M, Baghervand Navid R. Effects of date fruit (Phoenix dactylifera L.) on labor and delivery outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2020 Apr 14;20(1):210. PubMed
  8. Al Jaouni SK, Hussein A, Alghamdi N, et al. Effects of Phoenix dactylifera Ajwa on infection, hospitalization, and survival among pediatric cancer patients in a university hospital: A nonrandomized controlled trial. Integr Cancer Ther. 2019;18:15347354198
  9. Royani I, As'ad S, Mappaware NA, Hatta M, Rabia. Effect of Ajwa dates consumption to inhibit the progression of preeclampsia threats on mean arterial pressure and roll-over test. Biomed Res Int. 2019 Dec 10;2019:2917895. PubMed

See these in context on the Date Palm monograph →

Bacillus Coagulans 20 references
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  4. Kalima P, Masterton RG, Roddie PH, et al. Lactobacillus rhamnosus infection in a child following bone marrow transplant. J Infect 1996;32:165-7. PubMed
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  11. Pruccoli G, Silvestro E, Pace Napoleone C, Aidala E, Garazzino S, Scolfaro C. Are probiotics safe? Bifidobacterium bacteremia in a child with severe heart failure. Infez Med. 2019;27(2):175-178.
  12. Sendil S, Shrimanker I, Mansoora Q, Goldman J, Nookala VK. Lactobacillus rhamnosus bacteremia in an immunocompromised renal transplant patient. Cureus. 2020;12(2):e6887. PubMed
  13. Albarillo FS, Shah U, Joyce C, Slade D. Lactobacillus rhamnosus Infection: A single-center 4-year descriptive analysis. J Glob Infect Dis. 2020;12(3):119-123. PubMed
  14. Pasala S, Singer L, Arshad T, Roach K. Lactobacillus endocarditis in a healthy patient with probiotic use. IDCases. 2020;22:e00915. PubMed
  15. Agrawal S, Tuchman ES, Bruce MJ, Theodorou ME. Fatal Lactobacillus endocarditis in a patient with transcatheter aortic valve replacement. BMJ Case Rep. 2020;13(11):e236835.
  16. Antoun M, Hattab Y, Akhrass FA, Hamilton LD. Uncommon pathogen, Lactobacillus, causing infective endocarditis: Case report and review. Case Rep Infect Dis. 2020;2020:8833948. PubMed
  17. Rossi F, Amadoro C, Gasperi M, Colavita G. Lactobacilli infection case reports in the last three years and safety implications. Nutrients. 2022;14(6):1178. PubMed
  18. Franko B, Vaillant M, Recule C, Vautrin E, et al. Lactobacillus paracasei endocarditis in a consumer of probiotics. Med Mal Infect. 2013;43(4):171-3. PubMed
  19. Campbell RE, Miller A, Afroze A. Native valve endocarditis secondary to Lactobacillus paracasei bacteremia. Consultant. 2020;60(9):27-8. DOI
  20. Kato K, Funabashi N, Takaoka H, et al. Lactobacillus paracasei endocarditis in a consumer of probiotics with advanced and severe bicuspid aortic valve stenosis complicated with diffuse left ventricular mid-layer fibrosis. Int J Cardiol. 2016;224:157-161. PubMed

See these in context on the Bacillus Coagulans monograph →

Guar Gum 26 references
  1. Gin H, Orgerie MB, Aubertin J. The influence of Guar gum on absorption of metformin from the gut in healthy volunteers. Horm Metab Res 1989;21:81-3.
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  10. Chuang LM, Jou TS, Yang WS, et al. Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus. J Formos Med Assoc 1992;91:15-9.
  11. Ebeling P, Yki-Jarvinen H, Aro A, et al. Glucose and lipid metabolism and insulin sensitivity in type 1 diabetes: the effect of guar gum. Am J Clin Nutr 1988;48:98-103. PubMed
  12. Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996;30:359-71. PubMed
  13. Knopp RH, Superko HR, Davidson M, et al. Long-term blood cholesterol-lowering effects of a dietary fiber supplement. Am J Prev Med 1999;17:18-23. PubMed
  14. Patrick PG, Gohman SM, Marx SC, et al. Effect of supplements of partially hydrolyzed guar gum on the occurrence of constipation and use of laxative agents. J Am Diet Assoc 1998;98:912-4. PubMed
  15. Osterlund P, Ruotsalainen T, Korpela R, et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer 2007;97:1028-34. PubMed
  16. Lembcke B, Hasler K, Kramer P, et al. Plasma digoxin concentrations during administration of dietary fibre (guar gum) in man. Z Gastroenterol 1982;20;164-7.
  17. Riikonen, S., Savonius, H., Gylling, H., Nikkila, K., Tuomi, A. M., and Miettinen, T. A. Oral guar gum, a gel-forming dietary fiber relieves pruritus in intrahepatic cholestasis of pregnancy. Acta Obstet.Gynecol.Scand. 2000;79(4):260-264. DOI
  18. Kovacs, E. M., Westerterp-Plantenga, M. S., Saris, W. H., Goossens, I., Geurten, P., and Brouns, F. The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. Int.J.Obes.Relat Metab Disord. 2001;25(3):307 PubMed
  19. Halama, W. H. and Mauldin, J. L. Distal esophageal obstruction due to a guar gum preparation (Cal-Ban 3000). South.Med.J. 1992;85(6):642-645. PubMed
  20. Landin, K., Holm, G., Tengborn, L., and Smith, U. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. Am.J.Clin.Nutr. 1992;56(6):1061-1065. PubMed
  21. Cicero, A. F., Derosa, G., Manca, M., Bove, M., Borghi, C., and Gaddi, A. V. Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial. Clin.Exp.Hyp PubMed
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  23. Salenius JP, Harju E, Jokela H, et al. Long term effects of guar gum on lipid metabolism after carotid endarterectomy. BMJ 1-14-1995;310:95-96. PubMed
  24. Gylling, H., Riikonen, S., Nikkila, K., Savonius, H., and Miettinen, T. A. Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non-cholesterol sterols. Eur.J.Clin.Invest 1998;28(5):35 PubMed
  25. Brillantino A, Iacobellis F, Izzo G, et al. Maintenance therapy with partially hydrolyzed guar gum in the conservative treatment of chronic anal fissure: results of a prospective, randomized study. Biomed Res Int 2014;2014:964942. PubMed
  26. Polymeros D, Beintaris I, Gaglia A, et al. Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation. Dig Dis Sci 2014;59(9):2207-14. PubMed

See these in context on the Guar Gum monograph →

Lactobacillus Acidophilus 15 references
  1. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  2. Begtrup LM, de Muckadell OB, Kjeldsen J, Christensen RD, Jarbøl DE. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome--a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol 2013;48(10):1127-35 PubMed
  3. Chatterjee S, Kar P, Das T, Ray S, Gangulyt S, Rajendiran C, Mitra M. Randomised placebo-controlled double blind multicentric trial on efficacy and safety of Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 for prevention of antibiotic-associated
  4. Shavakhi A, Tabesh E, Yaghoutkar A, Hashemi H, Tabesh F, Khodadoostan M,Minakari M, Shavakhi S, Gholamrezaei A. The effects of multistrain probiotic compound on bismuth-containing quadruple therapy for Helicobacter pylori infection: a randomized placebo-c
  5. Karamali M, Dadkhah F, Sadrkhanlou M, et al. Effects of probiotic supplementation on glycaemic control and lipid profiles in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Metab 2016;42(4):234-41. PubMed
  6. Badehnoosh B, Karamali M, Zarrati M, et al. The effects of probiotic supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes. J Matern Fetal Neonatal Med. 2018 May;31(9):1128-1136.
  7. Kumar S, Kumar R, Rohilla L, Jacob N, Yadav J, Sachdeva N. A high potency multi-strain probiotic improves glycemic control in children with new-onset type 1 diabetes mellitus: A randomized, double-blind, and placebo-controlled pilot study. Pediatr Diabete
  8. Shahriari A, Karimi E, Shahriari M, Aslani N, Khooshideh M, Arab A. The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial PubMed
  9. Xiao SD, Zhang DZ, Lu H, et al. Multicenter, randomized, controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrhea. Adv Ther. 2003;20(5):253-60.
  10. Rossi F, Amadoro C, Gasperi M, Colavita G. Lactobacilli infection case reports in the last three years and safety implications. Nutrients. 2022;14(6):1178. PubMed
  11. Ozer M, Goksu SY, Shahverdiani A, Mustafa M. Lactobacillus acidophilus-induced endocarditis and associated splenic abscess. Case Rep Infect Dis 2020;2020:1382709.
  12. Sadrin S, Sennoune S, Gout B, et al. A 2-strain mixture of Lactobacillus acidophilus in the treatment of irritable bowel syndrome: A placebo-controlled randomized clinical trial. Dig Liver Dis 2020;52(5):534-540. PubMed
  13. Stoffer JN, Slingsby TJ, Giuliari GP. Lactobacillus acidophilus endophthalmitis after intravitreal bevacizumab injection requiring intraocular lens explantation. Can J Ophthalmol 2022;57(1):e21-e22. PubMed
  14. Cukovic-Cavka S, Likic R, Francetic I, Rustemovic N, Opacic M, Vucelic B. Lactobacillus acidophilus as a cause of liver abscess in a NOD2/CARD15-positive patient with Crohn's disease. Digestion 2006;73(2-3):107-10.
  15. Hui J, Ren Y, Wang Y, Han Q. Lactobacillus acidophilus endophthalmitis postcataract operation: A case report with a literature review. Ocul Immunol Inflamm 2023.

See these in context on the Lactobacillus Acidophilus monograph →

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

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