Major interaction on record — check this product against your medications before combining. Check your meds →
Dietary supplement

Coloclear Extra Ingredients & Drug Interactions

by Higher Nature

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

First and foremost: checking Coloclear Extra 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

Coloclear Extra is a dietary supplement by Higher Nature with 7 active ingredients. Its ingredients are commonly taken for constipation, irritable bowel syndrome (ibs), diarrhea.Based on those ingredients, 1,376 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Licorice, Clove, Fennel. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Coloclear Extra by Higher Nature

Ask about any prescription or over-the-counter medication and we check it for interactions with Coloclear Extra by Higher Nature — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Coloclear Extra by Higher Nature

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 12, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

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

Why this rating?
  • The label discloses an exact amount for 6 of its 7 active ingredients.

Coloclear Extra contains seven active ingredients chosen for digestive support. Bacillus coagulans is a spore-forming probiotic (live beneficial bacteria).

Licorice, fenugreek, aloe vera extract, fennel, clove, and brown flaxseed are all plant-derived; they're included for their traditional roles in digestive health and general wellness. The capsule also contains inactive ingredients like cellulose, magnesium stearate, and silicon dioxide, which are binders and flow agents.

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: Digestive health and bowel regularity.
  • We looked for evidence on: Constipation, Diarrhea, Dyspepsia, Flatulence, Colic, Clostridioides difficile infection — and 4 related terms.
  • The strongest evidence on file: Aloe is rated "Possibly Effective" for Constipation (Natural Medicines).
  • Also on file: Flaxseed is rated "Possibly Effective" for Constipation.
  • Also on file: Bacillus Coagulans is rated "Possibly Effective" for Constipation, Irritable bowel syndrome (IBS).

The evidence for this product's ingredients is mixed. Bacillus coagulans is possibly effective for constipation and irritable bowel syndrome (IBS), though the evidence isn't strong.

Licorice is possibly effective for canker sores and atopic dermatitis (eczema). Fenugreek is possibly effective for dysmenorrhea (period pain), sexual function, and diabetes.

Aloe is possibly effective for constipation, burns, diabetes, and psoriasis. Fennel is possibly effective for dysmenorrhea.

Clove is possibly effective for ventilator-associated pneumonia (a hospital-related condition), though this isn't relevant to most users. Flaxseed is possibly effective for high cholesterol, diabetes, breast pain, high blood pressure, and constipation.

For other proposed uses listed on the label or in marketing, the evidence isn't established in our data.

The evidence, ingredient by ingredient Bacillus Coagulans Licorice Fenugreek Aloe Fennel Clove Flaxseed

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 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 7 of 7.
  • General safety write-ups exist for 7 of 7.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these ingredients are generally well tolerated at food amounts, but this is a supplement with concentrated doses. Licorice can cause headache, nausea, and vomiting, and high doses or long-term use may cause serious problems like fluid retention and high blood pressure.

Aloe latex (the yellow substance under the leaf skin) can cause abdominal pain, cramps, and diarrhea; long-term use risks electrolyte imbalances and muscle weakness. Fenugreek may cause abdominal pain, bloating, diarrhea, and gas, and in rare cases severe allergic reactions.

Fennel and clove are generally well tolerated as spices but can cause gastrointestinal upset and allergic reactions in sensitive people. Flaxseed commonly causes bloating, gas, and diarrhea, especially at higher doses — drinking plenty of water helps.

Bacillus coagulans is generally well tolerated in healthy people, but there is a theoretical risk in people with central lines, severe illness, or weakened immune systems.

Side effects, ingredient by ingredient Bacillus Coagulans Licorice Fenugreek Aloe Fennel Clove Flaxseed

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 7 of the 7 matched ingredients can interact with medications — Clove, Fennel, Aloe, Fenugreek, Licorice, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications.
  • For scale: 1,377 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 Coloclear Extra, check your medications if you take: heart medications like digoxin (Lanoxin) — this is the most serious concern; blood thinners or blood sugar drugs; blood pressure medications; theophylline (a breathing medication); seizure drugs like phenytoin (Dilantin); contraceptives or hormone replacement; or antibiotics. The interaction with aloe and digoxin is Major severity.

Most others are Moderate. Your pharmacist can help you determine if timing or dose adjustments are needed.

Check your own medication Run your meds through the checker above

The bottom line

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

This product may help with constipation and IBS, and its ingredients have some evidence for other digestive and metabolic uses. However, if you take heart medications (especially digoxin), blood thinners, diabetes drugs, or seizure medications, you need to check this product against your prescriptions before starting — the interactions are real.

Talk with your pharmacist or doctor first, especially if you're pregnant, breastfeeding, or have a weakened immune system.

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

Assessment coverage: 7 of 7 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Apr 23, 2024.

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 Coloclear Extra, straight from the product label.

Brand Higher Nature
Barcode (UPC) 5031013103469
Net contents 180 Capsule(s)
Market status On market
Date entered into DSLD Apr 23, 2024
DSLD ID 304536
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Women (not pregnant or lactating), 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 Coloclear Extra by Higher Nature, 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 Capsule(s)
Maximum serving Sizes:
3 Capsule(s)
Servings per container
60
UPC/BARCODE
5031013103469
IngredientAmount% DV
Bacillus coagulans0 NP--
Licorice90 mg--
Fenugreek150 mg--
Aloe vera extract30 mg--
Fennel150 mg--
Clove60 mg--
Brown Flaxseed900 mg--

Other ingredients: Brown Flaxseed, Powder, Hydroxypropyl Methylcellulose, Fennel, Powder, Fenugreek, Powder, Mixed Tocopherols, Licorice, Powder, Aloe vera Extract, Clove, Powder, Magnesium Stearate, Silicon Dioxide

Tap any ingredient to jump to its full detail below.

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

CFU= colony forming units

New improved

Body health

Formulation

No artificial colours, flavours or preservatives. No yeast, added sugar or salt.

This product has not been tested on animals.

Advanced formula Optimal benefit

Vegetarian and vegan

Precautions

Warning: Do not take if pregnant or breastfeeding. If taking any medication or have a medical condition, please consult your healthcare professional before using this product.

Do not exceed recommended daily intake. Food supplements should not be used as a substitute for a varied and balanced diet and healthy lifestyle.

Storage: Store in a cool, dry place out of reach of children.

Formula

Flax fibre & aloe complex

Flax seed and aloe vera support normal bowel function and healthy digestion With friendly bacteria - bacillus coagulans

Suggested/Recommended/Usage/Directions

Directions: Adults take 3 capsules 1-3 times a day before a meal and with a large glass of water. Do not exceed recommended daily intake.

Storage

Storage: Store in a cool, dry place out of reach of children.

FDA Statement of Identity

Food Supplement

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

See for yourself

Coloclear Extra by Higher Nature label

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

Coloclear Extra 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 Coloclear Extra by Higher Nature

These are the 7 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Capsule(s) Dosage formCapsule Servings per container60 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.

Bacillus coagulans

Interacts with
182 drugs
0 NP per serving

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

Bacillus coagulans monograph & interactions

Licorice

Interacts with
1,040 drugs
90 mg per serving

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regu...

Licorice monograph & interactions

Fenugreek

Interacts with
389 drugs
150 mg per serving

Fenugreek is a common kitchen spice that is also taken as a supplement, mainly for blood sugar, cholesterol, and to support breast milk production. So...

Fenugreek monograph & interactions

Aloe vera extract

Interacts with
461 drugs
30 mg per serving

Aloe vera gel is widely used on the skin for minor burns and irritation, and some research suggests it may help. Aloe latex (the yellow part) is a str...

Aloe vera extract monograph & interactions

Fennel

Interacts with
740 drugs
150 mg per serving

Fennel is a Mediterranean herb widely used as a food and spice, and traditionally taken for digestive complaints, colic, and menstrual cramps. Some sm...

Fennel monograph & interactions

Clove

Interacts with
977 drugs
60 mg per serving

Clove is a common cooking spice that is also used in traditional medicine, especially as a topical numbing agent for tooth pain thanks to its main com...

Clove monograph & interactions

Brown Flaxseed

Interacts with
597 drugs
900 mg per serving

Flaxseed is a nutritious food rich in fiber, omega-3 fats (ALA), and plant compounds called lignans. It is most reliably helpful for constipation and...

Brown Flaxseed monograph & interactions

Other (inactive) ingredients: Brown Flaxseed, Powder, Hydroxypropyl Methylcellulose, Fennel, Powder, Fenugreek, Powder, Mixed Tocopherols, Licorice, Powder, Aloe vera Extract, Clove, Powder, Magnesium Stearate, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Coloclear Extra by Higher Nature Drug Interactions

Want to check YOUR meds against Coloclear Extra?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,376Drugs
1 Major 1,373 Moderate 2 Minor

Ingredients driving the most interactions

Licorice 1,040
Clove 977
Fennel 740
Brown Flaxseed 597
Aloe vera extract 461

Individual Drug Interactions

The ingredients in Coloclear Extra interact with 1,376 drugs. Click any drug to see the details.

7 of the 7 ingredients in Coloclear Extra interact with drugs. Each result below shows which ingredient is responsible. Licorice Clove Fennel Brown Flaxseed Aloe vera extract Fenugreek Bacillus coagulans

Each ingredient & the kinds of drugs it affects

For each ingredient in Coloclear Extra 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.

Licorice18 drug types · 1,040 drugs

Antihypertensive Drugs

Theoretically, licorice might reduce the effects of antihypertensive drugs.
In human research, licorice increases blood pressure in a dose-dependent manner.

Likelihood Possible Evidence B
Cisplatin (Platinol-Aq)

Theoretically, licorice might reduce the effects of cisplatin.
In animal research, licorice diminished the therapeutic efficacy of cisplatin.

Likelihood Possible Evidence D
Corticosteroids

Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids. Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice.

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

Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes. Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.

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

Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C8 (Cyp2C8) Substrates

Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.

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

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes. However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity. Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.

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

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Overuse of licorice might compound diuretic-induced potassium loss. In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month.

Likelihood Possible Evidence D
Estrogens

Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects.

Likelihood Possible Evidence D
Loop Diuretics

Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, licorice might decrease levels of midazolam.
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam. This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
In vitro research shows that licorice can increase P-glycoprotein activity.

Likelihood Possible Evidence D
Paclitaxel (Abraxane, Onxol)

Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice. Advise patients taking warfarin to avoid taking licorice.

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

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

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, licorice might increase levels of methotrexate.
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin. This interaction has not yet been reported in humans.

Likelihood Unlikely Evidence D
Licorice full monograph & interactions

Clove7 drug types · 977 drugs

Antidiabetes Drugs

Theoretically, concomitant use of clove extracts with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical and laboratory research suggest that polyphenol extracts from clove flower buds might lower blood glucose levels. Dosing adjustments for insulin or oral hypoglycemic agents may be necessary when taken with clove. Monitor blood glucose levels closely.

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

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP1A2 in a dose-dependent manner,. This effect has not been reported in humans.

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

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2C9.
In vitro research shows that eugenol, the principal constituent of clove, inhibits CYP2C9 in a dose-dependent manner. This effect has not been reported in humans.

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

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2D6.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP2D6 in a dose-dependent manner. This effect has not been reported in humans.

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

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP3A4.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP3A4 in a dose-dependent manner. This effect has not been reported in humans.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, clove oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Laboratory research suggests that eugenol, a constituent of clove, has antiplatelet activity. This interaction has not been reported in humans.

Likelihood Unlikely Evidence D
Ibuprofen (Advil, Others)

Theoretically, topical application of clove oil with ibuprofen might increase the absorption and side effects of topical ibuprofen.
Laboratory research shows that topical application of clove oil increases the absorption of topical ibuprofen. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Clove full monograph & interactions

Fennel6 drug types · 740 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Animal research suggests that fennel oil has antithrombotic and antiplatelet effects.

Likelihood Possible Evidence D
Ciprofloxacin (Cipro)

Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.

Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin.

Likelihood Probable Evidence D
Contraceptive Drugs

Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.

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

Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.

In vitro research suggests that fennel inhibits CYP3A4 enzyme activity. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.

Some constituents of fennel have estrogenic activity.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.

Some constituents of fennel have estrogenic activity, which may interfere with the antiestrogenic activity of tamoxifen.

Likelihood Possible Evidence D
Fennel full monograph & interactions

Brown Flaxseed5 drug types · 597 drugs

Antibiotic Drugs

Theoretically, antibiotics might interfere with the metabolism of flaxseed constituents, which could potentially alter the effects of flaxseed.
Some potential benefits of flaxseed are thought to be due to its lignan content. Secoisolariciresinol diglucoside (SDG), a major lignan precursor, is found in high concentrations in flaxseed. SDG is converted by bacteria in the colon to the lignans enterolactone and enterodiol. Antibiotics alter the flora of the colon, which could theoretically alter the metabolism of flaxseed.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, using flaxseed in combination with anticoagulant or antiplatelet drugs might have additive effects and increase the risk of bleeding.
Some clinical evidence suggests that the oil contained in flaxseed can decrease platelet aggregation.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, flaxseed might have additive effects when used with antidiabetes drugs and increase the risk for hypoglycemia.
Some clinical research suggests that flaxseed can lower blood glucose levels.

Likelihood Probable Evidence B
Antihypertensive Drugs

Theoretically, flaxseed might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
Clinical research shows that daily flaxseed consumption, especially for longer than 12 weeks, modestly reduces blood pressure.

Likelihood Possible Evidence D
Estrogens

Theoretically, taking flaxseed might decrease the effects of estrogens.
Flaxseed contains lignans with mild estrogenic and possible antiestrogenic effects. The lignans seem to compete with circulating endogenous estrogen and might reduce estrogen binding to estrogen receptors, resulting in an anti-estrogen effect. It is unclear if this effect transfers to exogenously administered estrogens.

Likelihood Possible Evidence D
Brown Flaxseed full monograph & interactions

Aloe vera extract7 drug types · 461 drugs

Digoxin (Lanoxin)

Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.
Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin.

Likelihood Possible Evidence D
Antidiabetes Drugs

Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Preliminary clinical research suggests aloe gel might lower blood glucose levels and have additive effects when used with antidiabetes drugs. Monitor blood glucose levels closely.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.
Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia.

Likelihood Possible Evidence D
Stimulant Laxatives

Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.
Due to cathartic laxative effects of aloe latex, concomitant use with other stimulant laxatives might compound fluid and electrolyte loss.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.
Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.

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

Theoretically, aloe might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that aloe extract induces CYP1A2 enzymes.

Likelihood Possible Evidence D
Aloe vera extract full monograph & interactions

Fenugreek9 drug types · 389 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.
Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels .

Likelihood Unlikely Evidence B
Antidiabetes Drugs

Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.
Clinical research shows that fenugreek seed can reduce fasting blood glucose and 2-hour postprandial glucose levels in adults with type 2 diabetes.

Likelihood Probable Evidence B
Clopidogrel (Plavix)

Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.
Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11%.

Likelihood Possible Evidence D
Metoprolol (Toprol)

Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.
Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Theoretically, fenugreek might decrease plasma levels of phenytoin.
Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.
Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Theophylline

Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.
Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22%.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).
Some fenugreek constituents have antiplatelet effects, although these might not be present in concentrations that are clinically significant. In one case report, a patient taking warfarin experienced an increased INR when starting to take fenugreek in combination with boldo.

Likelihood Possible Evidence D
Antihypertensive Drugs

Fenugreek may also have an additive effect on blood pressure-lowering medications. Studies on animals have shown that fenugreek seed can decrease both systolic and diastolic blood pressure by up to 22% when combined with metoprolol. Therefore, it is essential to monitor your blood pressure regularly if you are taking fenugreek and metoprolol together or any other antihypertensive drugs.

Likelihood Possible Evidence C
Fenugreek full monograph & interactions

Bacillus coagulans1 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
Bacillus coagulans full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Coloclear Extra, from the product label.

Higher Nature

See all Higher Nature products
Name
Higher Nature Ltd (EU)
Street Address
Block 1, Blanchardstown Corporate Park, Ballycoolen Road
City
Dublin
ZipCode
D15 AKK1
Web Address
highernature.com
Pharmacist Counseling Corner

Coloclear Extra by Higher Nature: Common Questions

Does Coloclear Extra by Higher Nature interact with any medications?
Yes. Based on its ingredients, Coloclear Extra has a known interaction with 1,376 medications, including 1 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Coloclear Extra contains 7 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take Coloclear Extra if I'm pregnant?
This isn't a good idea. Licorice is unsafe in pregnancy, fenugreek is likely unsafe, aloe is possibly unsafe, and fennel is possibly unsafe due to potential hormone-like effects and uterine stimulation. Flaxseed is possibly unsafe. Talk with your doctor before using this product while pregnant.
Is this safe while breastfeeding?
The safety data is limited or mixed. Licorice should be avoided. Fenugreek is possibly safe and is sometimes used to boost milk supply, but discuss it with your provider first. Aloe, fennel, and flaxseed all lack enough reliable data — talk with your doctor or pharmacist to weigh the risks and benefits for your situation.
What's the probiotic (Bacillus coagulans) supposed to do?
It's a live microorganism meant to support healthy gut bacteria. The evidence shows it's possibly effective for constipation and IBS. If you're taking antibiotics, you'll need to space them apart from this product because the antibiotics can kill the probiotic bacteria.
Will Coloclear Extra help my constipation?
Several ingredients have some evidence for constipation: Bacillus coagulans, aloe, and flaxseed are all possibly effective. However, aloe and flaxseed can also cause diarrhea in some people, so the effect varies. Start with a small dose and see how your body responds.
What are the most common side effects?
The most likely ones are gastrointestinal — bloating, gas, diarrhea, and abdominal discomfort. These come mainly from the flaxseed and fenugreek. Drinking plenty of water and starting with a small dose can help. Licorice can cause headache and nausea.
Can I use this long-term?
There's no long-term safety data in our records for this specific product formula. Licorice shouldn't be used long-term at high doses because it can cause serious problems. If you're considering regular use, ask your pharmacist whether it's appropriate for your situation.

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

Not sure if Coloclear Extra is safe with your meds?

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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.

Coloclear Extra label
Go deeper

The Full Monographs Behind Coloclear Extra’s Ingredients

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

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

Licorice

Interacts with 1,040 drugs

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, whic...

Read the full Licorice monograph → Herb & supplement monograph

Fenugreek

Interacts with 389 drugs

Fenugreek is a common kitchen spice that is also taken as a supplement, mainly for blood sugar, cholesterol, and to support breast milk production. Some early research is encouraging for blo...

Read the full Fenugreek monograph → Herb & supplement monograph

Aloe

Interacts with 461 drugs

Aloe vera gel is widely used on the skin for minor burns and irritation, and some research suggests it may help. Aloe latex (the yellow part) is a strong laxative that can cause cramping and...

Read the full Aloe monograph → Herb & supplement monograph

Fennel

Interacts with 740 drugs

Fennel is a Mediterranean herb widely used as a food and spice, and traditionally taken for digestive complaints, colic, and menstrual cramps. Some small studies suggest possible benefit for...

Read the full Fennel monograph → Herb & supplement monograph

Clove

Interacts with 977 drugs

Clove is a common cooking spice that is also used in traditional medicine, especially as a topical numbing agent for tooth pain thanks to its main compound, eugenol. Food amounts are general...

Read the full Clove monograph → Herb & supplement monograph

Flaxseed

Interacts with 597 drugs

Flaxseed is a nutritious food rich in fiber, omega-3 fats (ALA), and plant compounds called lignans. It is most reliably helpful for constipation and may modestly lower cholesterol, but evid...

Read the full Flaxseed monograph →
Sources

Sources & How We Checked

Coloclear Extra'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 263 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.

Bacillus Coagulans 20 references
  1. Saxelin M, Chuang NH, Chassy B, et al. Lactobacilli and bacteremia in southern Finland 1989-1992. Clin Infect Dis 1996;22:564-6. PubMed
  2. Tynkkynen S, Singh KV, Varmanen P. Vancomycin resistance factor of Lactobacillus rhamnosus GG in relation to enterococcal vancomycin resistance (van) genes. Int J Food Microbiol 1998;41:195-204. PubMed
  3. Klein G, Zill E, Schindler R, et al. Peritonitis associated with vancomycin-resistant Lactobacillus rhamnosus in a continuous ambulatory peritoneal dialysis patient; organism identification, antibiotic therapy, and case report. J Clin Microbiol 1998;36:
  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
  5. Goldin BR. Health Benefits of probiotics. Br J Nutr 1998;80:S203-7. DOI
  6. Rautio M, Jousimies-Somer H, Kauma H, et al. Liver abscess due to Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin Infect Dis 1999;28:1159-60.
  7. MacGregor G, Smith AJ, Thakker B, Kinsella J. Yoghurt biotherapy: contraindicated in immunosuppressed patients? Postgrad Med J 2002;78:366-7. PubMed
  8. Land MH, Rouster-Stevens K, Woods CR, et al. Lactobacillus sepsis associated with probiotic therapy. Pediatrics 2005;115:178-81.
  9. De Groote MA, Frank DN, Dowell E, et al. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 2005;24:278-80. PubMed
  10. Vahabnezhad E, Mochon AB, Wozniak LJ, Ziring DA. Lactobacillus bacteremia associated with probiotic use in a pediatric patient with ulcerative colitis. J Clin Gastroenterol. 2013;47(5):437-9. PubMed
  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 →

Licorice 92 references
  1. Farese RV Jr, Biglieri EG, Shackleton CH, et al. Licorice-induced hypermineralocorticoidism. N Engl J Med 1991;325:1223-7. PubMed
  2. Sigurjonsdottir HA, Ragnarsson J, Franzson L, Sigurdsson G. Is blood pressure commonly raised by moderate consumption of liquorice? J Hum Hypertens 1995;9:345-8.
  3. Armanini D, Lewicka S, Pratesi C, et al. Further studies on the mechanism of the mineralocorticoid action of licorice in humans. J Endocrinol Invest 1996;19:624-9. PubMed
  4. Zhang YD, Lorenzo B, Reidenberg MM. Inhibition of 11 beta hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds. J Steroid Biochem Mol Biol 1994;49:81-5.
  5. Strandberg TE, Jarvenpaa AL, Vanhanen H, McKeigue PM. Birth outcome in relation to licorice consumption during pregnancy. Am J Epidemiol 2001;153:1085-8. PubMed
  6. Sigurjonsdottir HA, Franzson L, Manhem K, et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. J Hum Hypertens 2001;15:549-52. PubMed
  7. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50. PubMed
  8. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  9. Yoshida S, Takayama Y. Licorice-induced hypokalemia as a treatable cause of dropped head syndrome. Clin Neurol Neurosurg 2003;105:286-7.. PubMed
  10. Strandberg TE, Andersson S, Jarvenpaa AL, et al. Preterm birth and licorice consumption during pregnancy. Am J Epidemiol 2002;156:803-5.. PubMed
  11. Hussain RM. The sweet cake that reaches parts other cakes can't! Postgrad Med J 2003;79:115-6.. PubMed
  12. Morris DJ, Davis E, Latif SA. Licorice, tobacco chewing, and hypertension. N Engl J Med 1990;322:849-50. PubMed
  13. Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab 2003;88:2384-92. PubMed
  14. Westman EC, Guthrie GP. Licorice, tobacco chewing, and hypertension. N Engl J Med 1990;322:850. PubMed
  15. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  16. Yasue H, Itoh T, Mizuno Y, Harada E. Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. Intern Med 2007;46:575-8. PubMed
  17. Brayley J, Jones J. Life-threatening hypokalemia associated with excessive licorice ingestion (letter). Am J Psychiatry 1994;151:617-8. PubMed
  18. de Klerk GJ, Nieuwenhuis G, Beutler JJ. Hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ 1997;314:731-2.
  19. Dellow EL, Unwin RJ, Honour JW. Pontefract cakes can be bad for you: refractory hypertension and liquorice excess. Nephol Dial Transplant 1999;14:218-20. PubMed
  20. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003;78:767-8. PubMed
  21. Eriksson JW, Carlberg B, Hillom V. Life-threatening ventricular tachycardia due to liquorice-induced hypokalemia. J Intern Med 1999;245:307-10.
  22. Janse A, van Iersel M, Hoefnagels WH, Olde Rikker MG. The old lady who liked liquorice: hypertension due to chronic intoxication in a memory-impaired patient. Neth J Med 2005;63:149-50.
  23. Lin SH, Yang SS, Chau T, Halperin ML. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci 2003;325:153-6. PubMed
  24. van den Bosch AE, van der Klooster JM, Zuidgeest DM, et al. Severe hypokalemic paralysis and rhabdomyolysis due to ingestion of liquorice. Neth J Med 2005;63:146-8.
  25. van Uum SH. Liquorice and hypertension. Neth J Med 2005;63:119-20.
  26. Russo S, Mastropasqua M, Mosetti MA, et al. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol 2000;20:145-8. PubMed
  27. Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice - evaluation of health hazard. Food Chem Toxicol 1993;31:303-12. PubMed
  28. Sontia B, Mooney J, Gaudet L, Touyz RM. Pseudohyperaldosteronism, liquorice, and hypertension. J Clin Hypertens (Greenwich) 2008;10:153-7. PubMed
  29. Francini-Pesenti F, Puato M, Piccoli A, Brocadello F. Liquorice-induced hypokalaemia and water retention in the absence of hypertension. Phytother Res 2008;22:563-5. PubMed
  30. Lapi F, Gallo E, Bernasconi S, et al. Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products. Br J Clin Pharmacol 2008;66:572-4. PubMed
  31. Chen MF, Shimada F, Kato H, Yano S, Kanaoka M. Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Endocrinol Jpn 1990;37:331-41. PubMed
  32. Teelucksingh S, Mackie AD, Burt D, McIntyre MA, Brett L, Edwards CR. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 1990;335(8697):1060-3. PubMed
  33. Heidemann HT, Kreuzfelder E. Hypokalemic rhabdomyolysis with myoglobinuria due to licorice ingestion and diuretic treatment. Klin Wochenschr 1983;61:303-5. PubMed
  34. Hukkanen J, Ukkola O, Savolainen MJ. Effects of low-dose liquorice alone or in combination with hydrochlorothiazide on the plasma potassium in healthy volunteers. Blood Press 2009;18:192-5. PubMed
  35. Bisogni V, Rossi GP, Calò LA. Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology. Blood Press. 2014 Jun;23(3):189-92. PubMed
  36. Dehours E, Vallé B, Rougé-Bugat ME, Florent B, Bounes V, Franchitto N. Suspected hypokalaemia following liquorice ingestion on board ship. J Telemed Telecare. 2013 Jun;19(4):227-8. PubMed
  37. Kormann R, Languille E, Amiot HM, Hertig A. Dying for a cup of tea. BMJ Case Rep. 2012 Oct 19;2012. PubMed
  38. Panduranga P, Al-Rawahi N. Licorice-induced severe hypokalemia with recurrent torsade de pointes. Ann Noninvasive Electrocardiol. 2013 Nov;18(6):593-6. PubMed
  39. Räikkönen K, Seckl JR, Heinonen K, Pyhälä R, Feldt K, Jones A, Pesonen AK, Phillips DI, Lahti J, Järvenpää AL, Eriksson JG, Matthews KA, Strandberg TE, Kajantie E. Maternal prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis fu
  40. Robles BJ, Sandoval AR, Dardon JD, Blas CA. Lethal liquorice lollies (liquorice abuse causing pseudohyperaldosteronism). BMJ Case Rep. 2013 Sep 19;2013. PubMed
  41. Chamberlain, J. J. and Abolnik, I. Z. Pulmonary edema following a licorice binge. West J Med 1997;167(3):184-185.
  42. Barrella, M., Lauria, G., Quatrale, R., and Paolino, E. Hypokaliemic rhabdomyolysis associated with liquorice ingestion: report of an atypical case. Ital.J Neurol.Sci 1997;18(4):217-220. PubMed
  43. Fugh-Berman, A. Herb-drug interactions. Lancet 2000;355(9198):134-138. PubMed
  44. Hasegawa, J., Suyama, Y., Kinugawa, T., Morisawa, T., and Kishimoto, Y. Echocardiographic findings of the heart resembling dilated cardiomyopathy during hypokalemic myopathy due to licorice-induced pseudoaldosteronism. Cardiovasc.Drugs Ther 1998;12(6):59 PubMed
  45. van Rossum, T. G., Vulto, A. G., Hop, W. C., Brouwer, J. T., Niesters, H. G., and Schalm, S. W. Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial. J Gastroenterol Hepatol 199 PubMed
  46. Lozano, P., Flores, D., Martinez, S., Artigues, I., Rimbau, E. M., and Gomez, F. Upper limb ischemia induced by chronic licorice ingestion. J Cardiovasc.Surg (Torino) 2000;41(4):631-632.
  47. Brouwers, A. J. and van der, Meulen J. ['Licorice hypertension' also caused by licorice tea]. Ned.Tijdschr Geneeskd. 4-14-2001;145(15):744-747.
  48. van Rossum, T. G., Vulto, A. G., Hop, W. C., and Schalm, S. W. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 2001;96(8):2432-2437. PubMed
  49. Sigurjonsdottir, H. A., Manhem, K., Axelson, M., and Wallerstedt, S. Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice. J Hum Hypertens 2003;17(2):125-131.
  50. Shintani, S., Murase, H., Tsukagoshi, H., and Shiigai, T. Glycyrrhizin (licorice)-induced hypokalemic myopathy. Report of 2 cases and review of the literature. Eur Neurol 1992;32(1):44-51. PubMed
  51. Chen, M. F., Shimada, F., Kato, H., Yano, S., and Kanaoka, M. Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. Endocrinol Jpn 1991;38(2):167-174. PubMed
  52. Lee, C. K., Park, K. K., Lim, S. S., Park, J. H., and Chung, W. Y. Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Biol Pharm Bull 2007;30(11):2191-2195. PubMed
  53. Isaia, G. C., Pellissetto, C., Ravazzoli, M., and Tamone, C. Acute adrenal crisis and hypercalcemia in a patient assuming high liquorice doses. Minerva Med 2008;99(1):91-94.
  54. Bocker, D. and Breithardt, G. [Induction of arrhythmia by licorice abuse]. Z Kardiol 1991;80(6):389-391.
  55. Tacconi, P., Paribello, A., Cannas, A., and Marrosu, M. G. Carpal tunnel syndrome triggered by excessive licorice consumption. J Peripher.Nerv.Syst. 2009;14(1):64-65. PubMed
  56. Tu, J. H., He, Y. J., Chen, Y., Fan, L., Zhang, W., Tan, Z. R., Huang, Y. F., Guo, D., Hu, D. L., Wang, D., and Hong-Hao Zhou. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010;66(8):805-810. PubMed
  57. Goultschin, J., Palmon, S., Shapira, L., Brayer, L., and Gedalia, I. Effect of glycyrrhizin-containing toothpaste on dental plaque reduction and gingival health in humans. A pilot study. J Clin Periodontol 1991;18(3):210-212. PubMed
  58. Scali, M., Pratesi, C., Zennaro, M. C., Zampollo, V., and Armanini, D. Pseudohyperaldosteronism from liquorice-containing laxatives. J Endocrinol Invest 1990;13(10):847-848. PubMed
  59. Chatterjee, N., Domoto-Reilly, K., Fecci, P. E., Schwamm, L. H., and Singhal, A. B. Licorice-associated reversible cerebral vasoconstriction with PRES. Neurology 2010;75(21):1939-1941. PubMed
  60. Imtiaz, K. E. Sweet root, bitter pill: liquorice-induced hyperaldosteronism. QJM 2011;104(12):1093-1095. PubMed
  61. van Beers, E. J., Stam, J., and van den Bergh, W. M. Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report. Crit Care 2011;15(1):R64. PubMed
  62. MacKenzie, M. A., Hoefnagels, W. H., Jansen, R. W., Benraad, T. J., and Kloppenborg, P. W. The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers. J Clin Endocrinol Metab 1990;70(6):1637-1643. PubMed
  63. Bardhan, K. D., Cumberland, D. C., Dixon, R. A., and Holdsworth, C. D. Clinical trial of deglycyrrhizinised liquorice in gastric ulcer. Gut 1978;19(9):779-782. PubMed
  64. Koster, M. and David, G. K. Reversible severe hypertension due to licorice ingestion. N Engl J Med 1968;278(25):1381-1383. PubMed
  65. Corse, F. M., Galgani, S., Gasparini, C., Giacanelli, M., and Piazza, G. Acute hypokalemic myopathy due to chronic licorice ingestion: report of a case. Ital J Neurol Sci 1983;4(4):493-497. PubMed
  66. Berlango Jimenez A., Jimenez Murillo L., Montero Perez F. J., Munoz Avila J. A., Torres Murillo J., and Calderon de la Barca Gazquez J. M. [Acute rhabdomyolysis and tetraparesis secondary to hypokalemia due to ingested licorice]. An Med Interna 1995;12(1)
  67. Bernardi, M., D'Intino, P. E., Trevisani, F., Cantelli-Forti, G., Raggi, M. A., Turchetto, E., and Gasbarrini, G. Effects of prolonged ingestion of graded doses of licorice by healthy volunteers. Life Sci 1994;55(11):863-872. PubMed
  68. van der Zwan A. Hypertension encephalopathy after liquorice ingestion. Clin Neurol Neurosurg 1993;95(1):35-37. PubMed
  69. Werner, S., Brismar, K., and Olsson, S. Hyperprolactinaemia and liquorice. Lancet 2-10-1979;1(8111):319.
  70. Nishioka, K. and Seguchi, T. Contact allergy due to oil-soluble licorice extracts in cosmetic products. Contact Dermatitis 1999;40(1):56. PubMed
  71. Yoshino T, Yanagawa T, Watanabe K. Risk factors for pseudoaldosteronism with rhabdomyolysis caused by consumption of drugs containing licorice and differences between incidence of these conditions in Japan and other countries: case report and literature r
  72. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
  73. Li J, Fan X, Wang Q. Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin: a case report. Medicine (Baltimore) 2018;97(11):e0073. PubMed
  74. Foster CA, Church KS, Poddar M, Van Uum SH, Spaic T. Licorice-induced hypertension: a case of pseudohyperaldosteronism due to jelly bean ingestion. Postgrad Med 2017;129(3):329-31. PubMed
  75. Gallacher SD, Tsokolas G, Dimitropoulos I. Liquorice-induced apparent mineralocorticoid excess presenting in the emergency department. Clin Med (Lond) 2017;17(1):43-5. PubMed
  76. Dai DW, Singh I, Hershman JM. Lozenge-induced hypermineralcorticoid state--a unique case of licorice lozenges resulting in hypertension and hypokalemia. J Clin Hypertens (Greenwich) 2016;18(2):159-60.
  77. O'Connell K, Kinsella J, McMahon C, Holian J, O'Riordan S. Posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption. Ir J Med Sci 2016;185(4):945-7. PubMed
  78. Hataya Y, Oba A, Yamashita T, Komatsu Y. Hyponatremia in an elderly patient due to isolated hypoaldosteronism occurring after licorice withdrawal. Intern Med 2017;56(2):175-9. PubMed
  79. Ha Y, Wang T, Li J, et al. Herb-Drug Interaction Potential of Licorice Extract and Paclitaxel: A Pharmacokinetic Study in Rats. Eur J Drug Metab Pharmacokinet. 2020;45(2):257-264. PubMed
  80. Edelman ER, Butala NM, Avery LL, Lundquist AL, Dighe AS. Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest. N Engl J Med. 2020;383(13):1263-1275. PubMed
  81. Wang H, Dong L, Qu F, et al. Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism. Pharm Biol. 2020 Dec;58(1):352-356. PubMed
  82. Attou R, Redant S, Honore PM, Preseau T, Hantson P, De Bels D. Liquorice intoxication can lead to cardiac arrest! Case Rep Emerg Med. 2020;2020:3727682. PubMed
  83. Benge E, Shah P, Yamaguchi L, Josef V. Trick or Treat? Licorice-Induced Hypokalemia: A Case Report. Cureus 2020;12(11):e11656. PubMed
  84. Abe K, Higurashi T, Takahashi M, et al. Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity. In Vivo 2021;35(4):2163-2169. PubMed
  85. Awad N, Makar G, Burroughs V, Ravi P, Burroughs SR. Licorice-induced apparent mineralocorticoid excess causing persistent hypertension and hypokalemia. Acta Endocrinol (Buchar) 2020;16(4):508-510. PubMed
  86. Patel P, Aknouk M, Dawson A, et al. How Much Is Too Much? Exploring Pseudohyperaldosteronism in Glycyrrhizic Acid Toxicity From Chronic Licorice Root Consumption. Cureus 2021;13(7):e16454. PubMed
  87. Fan ZJ, Liu JM, Li XX, et al. Glycyrrhizin-Induced Pseudohyperaldosteronism: A Case Report. Chin J Integr Med 2022. PubMed
  88. Gatica-Ortega ME, Pastor-Nieto MA. Allergic contact dermatitis to Glycyrrhiza inflata root extract in an anti-acne cosmetic product. Contact Dermatitis 2021;85(4):454-455.
  89. Wang JB, Huang A, Wang Y, et al. Corticosteroid plus glycyrrhizin therapy for chronic drug- or herb-induced liver injury achieves biochemical and histological improvements: a randomised open-label trial. Aliment Pharmacol Ther 2022;55(10):1297-1310. PubMed
  90. Puaratanaarunkon T, Washrawirul C, Chuenboonngarm N, Noppakun N, Asawanonda P, Kumtornrut C. Efficacy and safety of a facial serum containing snail secretion filtrate, Calendula officinalis, and Glycyrrhiza glaba root extract in the treatment of maskne: A
  91. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  92. Han EJ, Park JS. Lethal Arrhythmia Induced by Licorice. J Korean Med Sci 2023;38(12):e107. PubMed

See these in context on the Licorice monograph →

Fenugreek 30 references
  1. Madar Z, Thorne R. Dietary fiber. Prog Food Nutr Sci 1987;11:153-74.
  2. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:301-6.
  3. Patil SP, Niphadkar PV, Bapat MM. Allergy to fenugreek (Trigonella foenum graecum). Ann Allergy Asthma Immunol 1997;78:297-300. PubMed
  4. Lambert J, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy 2001;21:509-12. PubMed
  5. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty PubMed
  6. Yalcin SS, Tekinalp G, Ozalp I. Peculiar odor of traditional food and maple syrup urine disease. Pediatr Int 1999;41:108-9. PubMed
  7. Sewell AC, Mosandl A, Bohles H. False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. N Engl J Med 1999;341:769.. PubMed
  8. Abdo MS, al-Kafawi AA. Experimental studies on the effect of Trigonella foenum-graecum (abstract). Planta Med 1969;17:14-8.
  9. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India 2001;49:1057-61.
  10. Gabay MP. Galactogogues: medications that induce lactation. J Hum Lact 2002;18:274-9. PubMed
  11. Chevassus H, Gaillard JB, Farret A, et al. A fenugreek seed extract selectively reduces spontaneous fat intake in overweight subjects. Eur J Clin Pharmacol 2010;66(5):449-55. PubMed
  12. Turkyilmaz C, Onal E, Hirfanoglu IM, et al. The effect of galactagogue herbal tea on breast milk production and short-term catch-up of birth weight in the first week of life. J Altern Complement Med 2011;17(2):139-42. PubMed
  13. Swafford S, Berens P. Effect of fenugreek on breast milk volume. Abstract presented at: 5th International Meeting of the Academy of Breastfeeding Medicine; September 11-13,2000, Tucson, Arizona.
  14. Abdel-Barry, J. A., Abdel-Hassan, I. A., Jawad, A. M., and al Hakiem, M. H. Hypoglycaemic effect of aqueous extract of the leaves of Trigonella foenum-graecum in healthy volunteers. East Mediterr.Health J 2000;6(1):83-88. DOI
  15. Parvizpur, A., Ahmadiani, A., and Kamalinejad, M. Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. J Ethnopharmacol 3-8-2006;104(1-2):108-112. PubMed
  16. Mora, A., Herrrera, A., Lopez, C., Dahbi, G., Mamani, R., Pita, J. M., Alonso, M. P., Llovo, J., Bernardez, M. I., Blanco, J. E., Blanco, M., and Blanco, J. Characteristics of the Shiga-toxin-producing enteroaggregative Escherichia coli O104:H4 German ou
  17. Blanco, J. [Stx2a-producing enteroaggregative Escherichia coli O104:H4-ST678. Microbiological diagnostic already, for this and other STEC/VTEC serotypes!]. Enferm.Infecc.Microbiol.Clin. 2012;30(2):84-89.
  18. Beutin, L. and Martin, A. Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift with regard to human pathogenicity of STEC strains. J Food Prot. 2012;75(2):408-418. PubMed
  19. King LA, Nogareda F, Weill FX, Mariani-Kurkdjian P, Loukiadis E, Gault G, Jourdan-DaSilva N, Bingen E, Macé M, Thevenot D, Ong N, Castor C, Noël H, Van Cauteren D, Charron M, Vaillant V, Aldabe B, Goulet V, Delmas G, Couturier E, Le Strat Y, Combe C, Delm
  20. Reeder C, Legrand A, O'Connor-Von SK. The Effect of Fenugreek on Milk Production and Prolactin Levels in Mothers of Preterm Infants. Clinical Lactation 2013;4(4):159-165. DOI
  21. Al-Jenoobi FI, Ahad A, Mahrous GM, Al-Mohizea AM, AlKharfy KM, Al-Suwayeh SA. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs. Pharm Biol 2015;53(2):296-300. PubMed
  22. Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a doubl
  23. Steels E, Rao A, Vitetta L. Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation. Phytother Res. 2011 Sep;25(9):1294-300.
  24. Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016 Dec 24;194:260-268. PubMed
  25. Ouzir M, El Bairi K, Amzazi S. Toxicological properties of fenugreek (Trigonella foenum graecum). Food Chem Toxicol. 2016 Oct;96:145-54. PubMed
  26. Khodamoradi K, Khosropanah MH, Ayati Z, et al. The Effects of Fenugreek on Cardiometabolic Risk Factors in Adults: A Systematic Review and Meta-analysis. Complement Ther Med. 2020;52:102416. PubMed
  27. Alkharfy K, Jan B, Alotaibi K, et al. Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model. Curr Drug Metab 2021;22(12):969-977. PubMed
  28. Bin Jardan YA, Ahad A, Raish M, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effects of garden cress, fenugreek and black seed on the pharmacodynamics of metoprolol: an herb-drug interaction study in rats with hypertension. Pharm Biol 2021;59(1):1088-1097. PubMed
  29. Al-Mohizea AM, Ahad A, El-Maghraby GM, et al. Effects of Nigella sativa, Lepidium sativum and Trigonella foenum-graecum on sildenafil disposition in beagle dogs. Eur J Drug Metab Pharmacokinet. 2015;40(2):219-24. PubMed
  30. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin pharmacokinetics in beagle dogs. Phytother Res. 2013;27(12):1800-4.

See these in context on the Fenugreek monograph →

Aloe 41 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Wichtl MW. Herbal Drugs and Phytopharmaceuticals. Ed. N.M. Bisset. Stuttgart: Medpharm GmbH Scientific Publishers, 1994.
  3. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  4. Nusko G, Schneider B, Schneider I, et al. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study. Gut 2000;46:651-5. PubMed
  5. Luyckx VA, Ballantine R, Claeys M, et al. Herbal remedy-associated acute renal failure secondary to Cape aloes. Am J Kidney Dis 2002;39:E13. PubMed
  6. Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S. Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats. J Med Food 2004;7:61-6.
  7. Williams MS, Burk M, Loprinzi CL, et al. Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys 1996;36:345-9. PubMed
  8. Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Pract 1999;49:823-8.
  9. Bottenberg MM, Wall GC, Harvey RL, Habib S. Oral aloe vera-induced hepatitis. Ann Pharmacother 2007;41:1740-3. PubMed
  10. Rabe C, Musch A, Schirmacher P, et al. Acute hepatitis induced by an Aloe vera preparation: a case report. World J Gastroenterol 2005;11:303-4. PubMed
  11. Kanat O, Ozet A, Ataergin S. Aloe vera-induced acute toxic hepatitis in a healthy young man. Eur J Int Med 2006;17:589. PubMed
  12. Mueller SO, Stopper H. Characterization of the genotoxicity of anthraquinones in mammalian cells. Biochim Biophys Acta 1999;1428:406-14. PubMed
  13. Schorkhuber M, Richter M, Dutter A, et al. Effect of anthraquinone laxatives on the proliferation and urokinase secretion of normal, premalignant and malignant colonic epithelial cells. Eur J Cancer 1998;34:1091-8. PubMed
  14. Yang HN, Kim DJ, Kim YM, et al. Aloe-induced toxic hepatitis. J Korean Med Sci 2010;25:492-5. PubMed
  15. Choonhakarn C, Busaracome P, Sripanidkulchai B, et al. A prospective, randomized clinical trial comparing topical aloe vera with 0.1% triamcinolone acetonide in mild to moderate plaque psoriasis. J.Eur.Acad.Dermatol.Venereol. 2010;24:168-72. PubMed
  16. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. IV. Mechanism of cathartic effect. (3). Biol Pharm Bull. 1994;17:495-7. PubMed
  17. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. V. Mechanism of cathartic effect. (4). Biol Pharm Bull. 1994;17:651-3. PubMed
  18. Nelemans FA. Clinical and toxicological aspects of anthraquinone laxatives. Pharmacology. 1976;14 Suppl 1:73-7. PubMed
  19. Paulsen E, Korsholm L, Brandrup F. A double-blind, placebo-controlled study of a commercial Aloe vera gel in the treatment of slight to moderate psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2005;19:326-31.
  20. Huseini HF, Kianbakht S, Hajiaghaee R, et al. Anti-hyperglycemic and anti-hypercholesterolemic effects of Aloe vera leaf gel in hyperlipidemic type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Planta Med. 2012;78:311-6
  21. Ferreira, M., Teixeira, M., Silva, E., and Selores, M. Allergic contact dermatitis to Aloe vera. Contact Dermatitis 2007;57(4):278-279.
  22. Choonhakarn, C., Busaracome, P., Sripanidkulchai, B., and Sarakarn, P. The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial. Br J Dermatol 2008;158(3):573-577. PubMed
  23. Baretta, Z., Ghiotto, C., Marino, D., and Jirillo, A. Aloe-induced hypokalemia in a patient with breast cancer during chemotherapy. Ann.Oncol. 2009;20(8):1445-1446. PubMed
  24. Hunter, D. and Frumkin, A. Adverse reactions to vitamin E and aloe vera preparations after dermabrasion and chemical peel. Cutis 1991;47(3):193-196.
  25. Alvarez-Perea, A., Garcia, A. P., Hernandez, A. L., de, Barrio M., and Baeza, M. L. Urticaria due to aloe vera: a new sensitizer? Ann.Allergy Asthma Immunol. 2010;105(5):404-405. PubMed
  26. Hogan, D. J. Widespread dermatitis after topical treatment of chronic leg ulcers and stasis dermatitis. CMAJ. 2-15-1988;138(4):336-338.
  27. Savchak VI. Acute bullous allergic dermatitis due to local application of aloe leaves. Vestnik Dermatologii i Venerologii 1977;12:44-45.
  28. Nakamura, T. and Kotajima, S. Contact dermatitis from aloe arborescens. Contact Dermatitis 1984;11(1):51. PubMed
  29. Shoji, A. Contact dermatitis to Aloe arborescens. Contact Dermatitis 1982;8(3):164-167. PubMed
  30. Morrow, D. M., Rapaport, M. J., and Strick, R. A. Hypersensitivity to aloe. Arch Dermatol. 1980;116(9):1064-1065. DOI
  31. Cosmetic Ingredient Review Expert Panel. Final report on the safety assessment of AloeAndongensis Extract, Aloe Andongensis Leaf Juice,aloe Arborescens Leaf Extract, Aloe Arborescens Leaf Juice, Aloe Arborescens Leaf Protoplasts, Aloe Barbadensis Flower E
  32. Bhalang K, Thunyakitpisal P, Rungsirisatean N. Acemannan, a polysaccharide extracted from Aloe vera, is effective in the treatment of oral aphthous ulceration. J Altern Complement Med 2013;19(5):429-34.
  33. Hajheydari Z, Saeedi M, Morteza-Semnani K, Soltani A. Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial. J Dermatolog Treat 2014;25(2):123-9.
  34. Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM. Euforia-induced acute hepatitis in a patient with scleroderma. BMJ Case Rep 2012;2012. PubMed
  35. Lee J, Lee MS, Nam KW. Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review. Korean J Gastroenterol 2014;64(1):54-8. PubMed
  36. Guo X, Mei N. Aloe Vera - A Review of Toxicity and Adverse Clinical Effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2016;34(2):77-96.
  37. Hoogenboom TCH, Patel N, Cook NA, Williams R, Taylor-Robinson SD, Lim AKP. The effect of Aloe vera juice on liver enzymes and hepatic structure in a healthy population. Integr Med (Encinitas) 2020;19(3):30-4.
  38. Mushtaq S, Mushtaq Z, Sarfraz J, et al. Comparison of effect of aloe vera gel with aspirin and celecoxib on platelet aggregation. Professional Med J. 2020; 27(5):973-978. DOI
  39. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  40. Sabbaghzadegan S, Soltani MH, Kamalinejad M, Bahrami M, Kabir A, Dadmehr M. The effect of a standardized capsule of Aloe vera gel on the quality of life in patients with systolic heart failure: A randomized double-blind placebo-controlled clinical trial.
  41. Lewis ED, Crowley DC, Guthrie N, Evans M. Healthy adults supplemented with a nutraceutical formulation containing Aloe vera gel, rosemary and Poria cocos enhances the effect of influenza vaccination in a randomized, triple-blind, placebo-controlled trial. PubMed

See these in context on the Aloe monograph →

Fennel 17 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Zhu M, Wong PY, Li RC. Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat. J Pharm Pharmacol 1999;51:1391-6.
  4. Gral N, Beani JC, Bonnot D, et al. [Plasma levels of psoralens after celery ingestion]. Ann Dermatol Venereol 1993;120:599-603.
  5. Burkhard PR, Burkhardt K, Haenggeli CA, Landis T. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246:667-70. PubMed
  6. Rosti L, Nardini A, Bettinelli ME, Rosti D. Toxic effects of a herbal tea mixture in two newborns. Acta Paediatrica 1994;83:683. PubMed
  7. Cuzzolin L, Zaffani S, and Benoni G. Safety implications regarding use of phytomedicines. Eur.J Clin Pharmacol. 2006;62:37-42. PubMed
  8. Tognolini, M., Ballabeni, V., Bertoni, S., Bruni, R., Impicciatore, M., and Barocelli, E. Protective effect of Foeniculum vulgare essential oil and anethole in an experimental model of thrombosis. Pharmacol.Res 2007;56(3):254-260. PubMed
  9. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  10. Tognolini, M., Barocelli, E., Ballabeni, V., Bruni, R., Bianchi, A., Chiavarini, M., and Impicciatore, M. Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity. Life Sci. 2-23-2006;78(13):1419-1432. PubMed
  11. Subehan, Zaidi, S. F., Kadota, S., and Tezuka, Y. Inhibition on human liver cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): identification and characterization of a mechanism-based inactivator. J Agric.Food Chem. 12-12-2007;55(25):101 PubMed
  12. LEVY, S. B. Bronchial asthma due to ingestion of fennel and fennel seed. Ann.Allergy 1948;6(4):415.
  13. Ottolenghi, A., De Chiara, A., Arrigoni, S., Terracciano, L., and De Amici, M. [Diagnosis of food allergy caused by fruit and vegetables in children with atopic dermatitis]. Pediatr Med Chir 1995;17(6):525-530.
  14. Trabace L, Tucci P, Ciuffreda L, et al. "Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm. J Ethnopharmacol. 2015;174:396-402. PubMed
  15. Denaxa D, Arkwright PD. Fennel as a cause of immediate hypersensitivity to toothpaste. Ann Allergy Asthma Immunol. 2020;125(1):99-100. PubMed
  16. Lee HW, Ang L, Lee MS, Alimoradi Z, Kim E. Fennel for reducing pain in primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials. Nutrients 2020;12(11):3438. PubMed
  17. Mathew T, John SK, Javali M, Vasireddy M, Nadig R, Sarma GRK. Substance use related cluster headache: A case series. Headache 2022;62(7):908-910. PubMed

See these in context on the Fennel monograph →

Clove 26 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  3. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. PubMed
  4. Chen SJ, Wang MH, Chen IJ. Antiplatelet and calcium inhibitory properties of eugenol and sodium eugenol acetate. Gen Pharmacol 1996;27:629-33. PubMed
  5. Malson JL, Lee EM, Murty R, et al. Clove cigarette smoking: biochemical, physiological, and subjective effects. Pharmacol Biochem Behav 2003;74:739-45. PubMed
  6. Kirsch CM, Yenokida GG, Jensen WA, et al. Non-cardiogenic pulmonary oedema due to the intravenous administration of clove oil. Thorax 1990;45:235-6. PubMed
  7. Pallares, D. E. Link between clove cigarettes and urticaria? Postgrad.Med 10-1-1999;106(4):153. PubMed
  8. Barnard, D. R. Repellency of essential oils to mosquitoes (Diptera: Culicidae). J Med Entomol. 1999;36(5):625-629. PubMed
  9. Sanchez-Perez, J. and Garcia-Diez, A. Occupational allergic contact dermatitis from eugenol, oil of cinnamon and oil of cloves in a physiotherapist. Contact Dermatitis 1999;41(6):346-347. PubMed
  10. Andersen, K. E., Johansen, J. D., Bruze, M., Frosch, P. J., Goossens, A., Lepoittevin, J. P., Rastogi, S., White, I., and Menne, T. The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals. Toxicol.Appl PubMed
  11. Alqareer, A., Alyahya, A., and Andersson, L. The effect of clove and benzocaine versus placebo as topical anesthetics. J Dent 2006;34(10):747-750. PubMed
  12. Lane, B. W., Ellenhorn, M. J., Hulbert, T. V., and McCarron, M. Clove oil ingestion in an infant. Hum.Exp Toxicol. 1991;10(4):291-294. PubMed
  13. Quirce, S., Fernandez-Nieto, M., del, Pozo, V, Sastre, B., and Sastre, J. Occupational asthma and rhinitis caused by eugenol in a hairdresser. Allergy 2008;63(1):137-138. PubMed
  14. Srivastava, K. C. and Malhotra, N. Acetyl eugenol, a component of oil of cloves (Syzygium aromaticum L.) inhibits aggregation and alters arachidonic acid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1991;42(1):73-81. PubMed
  15. Dyrbye, B. A., Dubois, L., Vink, R., and Horn, J. A patient with clove oil intoxication. Anaesth.Intensive Care 2012;40(2):365-366.
  16. Guidotti, T. L., Laing, L., and Prakash, U. B. Clove cigarettes. The basis for concern regarding health effects. West J Med 1989;151(2):220-228.
  17. Anonymous. Evaluation of the health hazard of clove cigarettes. Council on Scientific Affairs. JAMA 12-23-1988;260(24):3641-3644. DOI
  18. Romaguera, C., Alomar, A., Camarasa, J. M., Garcia, Bravo B., Garcia, Perez A., Grimalt, F., Guerra, P., Lopez, Gorretcher B., Pascual, A. M., Miranda, A., and . Contact dermatitis in children. Contact Dermatitis 1985;12(5):283-284. PubMed
  19. Hackett, P. H., Rodriguez, G., and Roach, R. C. Clove cigarettes and high-altitude pulmonary edema. JAMA 6-28-1985;253(24):3551-3552. DOI
  20. Isaacs, G. Permanent local anaesthesia and anhidrosis after clove oil spillage. Lancet 4-16-1983;1(8329):882. PubMed
  21. Saeed, S. A. and Gilani, A. H. Antithrombotic activity of clove oil. J Pak Med Assoc 1994;44(5):112-115.
  22. Hartnoll, G., Moore, D., and Douek, D. Near fatal ingestion of oil of cloves. Arch.Dis Child 1993;69(3):392-393. PubMed
  23. Srivastava, K. C. Antiplatelet principles from a food spice clove (Syzygium aromaticum L) [corrected]. Prostaglandins Leukot.Essent.Fatty Acids 1993;48(5):363-372.
  24. Jiang Q, Wu Y, Zhang H, et al. Development of essential oils as skin permeation enhancers: penetration enhancement effect and mechanism of action. Pharmaceutical Biol. 2017;55(1):1592-1600. PubMed
  25. Mohan R, Jose S, Mulakkal J, Karpinsky-Semper D, Swick AG, Krishnakumar IM. Water-soluble polyphenol-rich clove extract lowers pre- and post-prandial blood glucose levels in healthy and prediabetic volunteers: an open label pilot study. BMC Complement Alt PubMed
  26. Alharbi NFM, Ahad A, Bin Jardan YA, Al-Jenoobi FI. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Saudi Pharm J 2024;32(7):102118. PubMed

See these in context on the Clove monograph →

Flaxseed 37 references
  1. Kolonel LN, Nomura AM, Cooney RV. Dietary fat and prostate cancer: current status. J Natl Cancer Inst 1999;91:414-28. PubMed
  2. Ramon JM, Bou R, Romea S, et al. Dietary fat intake and prostate cancer risk: a case-control study in Spain. Cancer Causes Control 2000;11:679-85. PubMed
  3. Thompson LU, Rickard SE, Cheung F, et al. Variability in anticancer lignan levels in flaxseed. Nutr Cancer 1997;27:26-30. PubMed
  4. Nordstrom DC, Honkanen VE, Nasu Y, et al. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 1995;14:231-4. PubMed
  5. Cunnane SC, Ganguli S, Menard C, et al. High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Br J Nutr 1993;69:443-53.
  6. Clark WF, Parbtani A, Huff MW, et al. Flaxseed: a potential treatment for lupus nephritis. Kidney Int 1995;48:475-80. PubMed
  7. Cunnane SC, Hamadeh MJ, Liede AC, et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1995;61:62-8. PubMed
  8. De Stefani E, Deneo-Pellegrini H, Boffetta P, et al. Alpha-linolenic acid and risk of prostate cancer: a case-control study in Uruguay. Cancer Epidemiol Biomarkers Prev 2000;9:335-8.
  9. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993;85:1571-9. PubMed
  10. Clark WF, Kortas C, Heidenheim P, et al. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. J Am Coll Nutr 2001;20:143-8. PubMed
  11. Serraino M, Thompson LU. The effect of flaxseed supplementation on early risk markers for mammary carcinogenesis. Cancer Lett 1991;60:135-42. PubMed
  12. Rickard SE, Yuan YV, Thompson LU. Plasma insulin-like growth factor I levels in rats are reduced by dietary supplementation of flaxseed or its lignan secoisolariciresinol diglycoside. Cancer Lett 2000;161:47-55. PubMed
  13. Mousavi Y, Adlercreutz H. Enterolactone and estradiol inhibit each other's proliferative effect on MCF-7 breast cancer cells in culture. J Steroid Biochem Mol Biol 1992;41:615-9.. PubMed
  14. Adlercreutz H, Fotsis T, Bannwart C, et al. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem 1986;25:791-7.. PubMed
  15. Rose DP. Dietary fiber and breast cancer. Nutr Cancer 1990;13:1-8.. PubMed
  16. Lemay A, Dodin S, Kadri N, et al. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet Gynecol 2002;100:495-504.. DOI
  17. Brooks JD, Ward WE, Lewis JE, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004;79:318-25.. PubMed
  18. Laaksonen DE, Laukkanen JA, Niskanen L, et al. Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study. Int J Cancer 2004;111:444-50.. PubMed
  19. Dodin S, Lemay A, Jacques H, et al. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 2005 PubMed
  20. Brouwer IA, Katan MB, Zock PL. Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr 2004;134:919-22.
  21. Demark-Wahnefried W, Polascik TJ, George SL, et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev 2008;17:3577-87. PubMed
  22. Thompson LU, Chen JM, Li T, et al. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 2005;11:3828-35. PubMed
  23. Mani UV, Mani I, Biswas M, Kumar SN. An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus. J Diet Suppl 2011;8:257-65.
  24. Rhee Y, Brunt A. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design. Nutr J 2011;10:44. PubMed
  25. Cornish SM, Chilibeck PD, Paus-Jennsen L, et al. A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults. Appl Physiol Nutr Metab 2009;34:89-98. PubMed
  26. Cockerell KM, Watkins AS, Reeves LB, et al. Effects of linseeds on the symptoms of irritable bowel syndrome: a pilot randomised controlled trial. J Hum Nutr Diet 2012;25:435-43. PubMed
  27. Colli MC, Bracht A, Soares AA, et al. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms. J Med Food 2012;15:840-5. PubMed
  28. Allman, M. A., Pena, M. M., and Pang, D. Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function. Eur.J Clin.Nutr. 1995;49(3):169-178.
  29. Simbalista RL, Sauerbronn AV, Aldrighi JM, Areas JA. Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. J Nutr 2010;140:293-7. PubMed
  30. Patade A, Devareddy L, Lucas EA, et al. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. J Womens Health (Larchmt) 2008;17:355-66. PubMed
  31. Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, Maddaford TG, Ramjiawan B, Aliani M, Guzman R, Pierce GN. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension. 2013 Dec;62(6):1081-9. PubMed
  32. Bloedon LT, Balikai S, Chittams J, et al. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 2008;27:65-74. PubMed
  33. Ursoniu S, Sahebkar A, Andrica F, Serban C, Banach M; Lipid and Blood Pressure Meta-analysis Collaboration Group. Effects of flaxseed supplements on blood pressure: a systematic review and meta-analysis of controlled clinical trial. Clin Nutr. 2016 Jun;3 PubMed
  34. Mohammadi-Sartang M, Sohrabi Z, Barati-Bodaji R, Raeisi-Dehkordi H, Mazloom Z. Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials. Nutr Rev. 2018 Feb 1;76( PubMed
  35. Haidari F, Banaei-Jahromi N, Zakerkish M, Ahmadi K. The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial. Nutr J. 2020;19(1):8. PubMed
  36. Villarreal-Renteria AI, Herrera-Echauri DD, Rodríguez-Rocha NP, et al. Effect of flaxseed (Linum usitatissimum) supplementation on glycemic control and insulin resistance in prediabetes and type 2 diabetes: A systematic review and meta-analysis of randomi
  37. Li L, Li H, Gao Y, Vafaei S, Zhang X, Yang M. Effect of flaxseed supplementation on blood pressure: a systematic review, and dose-response meta-analysis of randomized clinical trials. Food Funct 2023;14(2):675-690. PubMed

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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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