Major interaction on record — check this product against your medications before combining. Based on 10 of 14 ingredients. Check your meds →
Dietary supplement

Cold-Zero Ingredients & Drug Interactions

by Nature's Health

Cold-Zero label
See full label image
Capsule Category: Botanical
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 Cold-Zero 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

Cold-Zero is a dietary supplement by Nature's Health with 14 active ingredients. Its ingredients are commonly taken for skin conditions like acne and eczema, digestive support, diuretic ('detox') and blood purifier.Based on those ingredients, 1,569 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Licorice, Bitter Orange, Peppermint. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Cold-Zero by Nature's Health

Ask about any prescription or over-the-counter medication and we check it for interactions with Cold-Zero by Nature's Health — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Cold-Zero by Nature's Health

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

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 11, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 0 of its 14 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (1,000 mg) without saying how much of each component you get.

Cold-Zero contains 14 ingredients, including a proprietary blend. The active ingredients are Burdock, Licorice, Peppermint, Costus, Tangerine, Perilla, Fritillaria, Japanese Mint, Balloon Flower, Kudzu, Ledebouriella, Corydalis, Bitter Orange, and Poria Mushroom.

These are traditional botanical components often used together in herbal cough and cold formulas. The product also contains gelatin as an inactive ingredient (the capsule material).

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: Healthy immune function and respiratory system support.
  • We looked for evidence on: Asthma, Atopic dermatitis (eczema), Bronchitis, Common cold, Cough, Allergic rhinitis (hay fever) — and 4 related terms.
  • The strongest evidence on file: Licorice is rated "Possibly Effective" for Atopic dermatitis (eczema) (Natural Medicines).
  • Also on file: Burdock is rated "Insufficient Reliable Evidence To Rate" for Common cold, Atopic dermatitis (eczema).
  • Also on file: Perilla is rated "Insufficient Reliable Evidence To Rate" for Allergic rhinitis (hay fever), Asthma, Common cold, Cough.

The evidence for most of Cold-Zero's ingredients is limited. Peppermint is rated Likely Effective for irritable bowel syndrome and Possibly Effective for indigestion and nausea — though that's not a cold symptom.

Licorice is Possibly Effective for eczema and canker sores. Kudzu is Possibly Effective for alcohol use disorder.

For the rest — Burdock, Costus, Tangerine, Perilla, Fritillaria, Japanese Mint, Balloon Flower, Ledebouriella, Corydalis, Bitter Orange, and Poria Mushroom — the evidence we hold rates them as having Insufficient Reliable Evidence for common cold, cough, or related conditions. If you're looking for help with a cold or cough, talk to your pharmacist about which ingredients, if any, are supported by data for your specific symptom.

The evidence, ingredient by ingredient Burdock Licorice Peppermint Costus Tangerine Perilla Japanese Mint Kudzu

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 10 of the 10 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 10 of 10.
  • General safety write-ups exist for 10 of 10.
  • 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 in typical use, but several carry cautions. Burdock is safe as a food short-term but should be avoided in supplement amounts during pregnancy due to potential uterine effects, and during breastfeeding there's not enough data.

Licorice is fine in food amounts but high-dose supplements can cause serious problems — the compound glycyrrhizin can raise blood pressure and lower potassium with long-term use. Avoid licorice supplements if you're pregnant or breastfeeding.

Peppermint tea and culinary amounts are safe, but concentrated oil should be used cautiously in pregnancy and breastfeeding. Bitter Orange carries a caution: it contains stimulant compounds that raise heart rate and blood pressure, especially risky in pregnancy or with heart conditions.

Kudzu, Costus, Perilla, Tangerine, Japanese Mint, and Poria Mushroom all have limited human safety data and are best avoided in pregnancy and breastfeeding unless your doctor approves.

Side effects, ingredient by ingredient Burdock Licorice Peppermint Costus Tangerine Perilla Japanese Mint Kudzu

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 10 matched ingredients can interact with medications — Burdock, Poria Mushroom, Peppermint, Kudzu, Licorice, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications.
  • For scale: 1,570 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 Cold-Zero, check with your pharmacist if you take monoamine oxidase inhibitors (MAOIs) — an older class of antidepressants — or midazolam (Versed, a sedative), as Bitter Orange poses Major-severity risks. Also double-check Moderate-severity interactions if you take blood thinners (especially warfarin), heart medications (digoxin), cancer drugs (cisplatin, paclitaxel), diabetes medications, estrogen or hormone therapy, sedatives, loop diuretics, immunosuppressants like cyclosporine, or drugs metabolized by liver enzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP3A4.

Check your own medication Run your meds through the checker above

The bottom line

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

Cold-Zero is a multi-ingredient herbal blend with several serious drug interactions — most notably with blood thinners, heart medications, sedatives, and antidepressants. If you take any prescription medications, especially for the heart, blood pressure, anxiety, or blood clotting, check with your pharmacist before using this product.

The evidence for effectiveness on colds or cough is not established in our data. Talk to your pharmacist about whether this blend is right for you and your medications.

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

Assessment coverage: 10 of 14 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated May 19, 2022.

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 Cold-Zero, straight from the product label.

Brand Nature's Health
Barcode (UPC) 698209135243
Net contents 90 Capsule(s)
Market status On market
Date entered into DSLD May 19, 2022
DSLD ID 263583
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Cold-Zero by Nature's Health, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
45
UPC/BARCODE
698209135243
IngredientAmount% DV
Proprietary Blend1000 mg--
Burdock0 NP--
Licorice0 NP--
Peppermint0 NP--
Costus0 NP--
Tangerine0 NP--
Perilla0 NP--
Fritillaria0 NP--
Japanese Mint0 NP--
Balloon Flower0 NP--
Kudzu0 NP--
Ledebouriella0 NP--
Corydalis0 NP--
Bitter Orange0 NP--
Poria Mushroom0 NP--

Other ingredients: Gelatin

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.
Suggested/Recommended/Usage/Directions

Suggested use: Take 2 capsules three times daily.

Formulation

Description: Cold-Zero may contribute to healthy immune function with its ingredients acting as antioxidants to neutralize free radicals and bolstering cellular defenses. Other components help maintain clear passageways throughout the respiratory tract.

All-natural herbal formula Immune support Blend of immune system supporting herbs Soothing support for respiratory system.

Free of wheat, gluten, milk, egg, soybeans, fish, shellfish, peanuts, and tree nuts. Contains no fillers, preservatives, artificial colors, flavors, or sweeteners.

Precautions

Caution: Do not exceed recommended dose.

Pregnant or nursing mothers, children under the age of 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement.

Pregnant or nursing mothers, children under the age of 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement.

Storage

Store at room temperature.

FDA Disclaimer Statement

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

FDA Statement of Identity

Dietary Supplement

Seals/Symbols

GMP Good Manufacturing Practice Made in USA

General Statements

500 mg

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

See for yourself

Cold-Zero by Nature's Health label

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

Cold-Zero 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 Cold-Zero by Nature's Health

These are the 14 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container45 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.

Proprietary Blend

1000 mg per serving

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

Interaction report

Cold-Zero by Nature's Health Drug Interactions

Want to check YOUR meds against Cold-Zero?

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
1,569Drugs
10 Major 1,538 Moderate 21 Minor

Ingredients driving the most interactions

Licorice 1,040
Bitter Orange 957
Peppermint 796
Tangerine 643
Kudzu 584

Individual Drug Interactions

The ingredients in Cold-Zero interact with 1,569 drugs. Click any drug to see the details.

7 of the 14 ingredients in Cold-Zero interact with drugs. Each result below shows which ingredient is responsible. Licorice Bitter Orange Peppermint Tangerine Kudzu Poria Mushroom Burdock

Each ingredient & the kinds of drugs it affects

For each ingredient in Cold-Zero 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

Bitter Orange13 drug types · 957 drugs

Midazolam (Versed)

Bitter orange might increase blood levels of midazolam.
One small clinical study shows that bitter orange juice can increase midazolam levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4). Theoretically, bitter orange might increase the risk of midazolam-related adverse effects.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.

Likelihood Probable Evidence D
Antidiabetes Drugs

Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs. However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone.

Likelihood Possible Evidence B
Caffeine

Bitter orange might increase blood pressure and heart rate when taken with caffeine.
Small clinical studies show that taking bitter orange in combination with caffeine can increase blood pressure and heart rate in otherwise healthy normotensive adults. Theoretically, this might increase the risk of serious cardiovascular adverse effects.

Likelihood Possible Evidence B
Colchicine

Bitter orange might affect colchicine levels.
Colchicine is a substrate of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Bitter orange has been reported to inhibit CYP3A4 and increase levels of CYP3A4 substrates. However, one small clinical study in healthy adults shows that drinking bitter orange juice 240 mL twice daily for 4 days and taking a single dose of colchicine 0.6 mg on the 4th day decreases colchicine peak serum levels by 24%, time to peak serum level by 1 hour, and overall exposure to colchicine by 20%. The clinical significance of this finding is unclear.

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

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.

Likelihood Possible Evidence B
Dextromethorphan (Robitussin Dm, Others)

Bitter orange might increase blood levels of dextromethorphan.
One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.

Likelihood Possible Evidence B
Felodipine (Plendil)

Bitter orange might increase blood levels of felodipine.
One small clinical study shows that bitter orange juice increases felodipine levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for felodipine-related adverse effects.

Likelihood Probable Evidence B
Indinavir (Crixivan)

Bitter orange might increase blood levels of indinavir.
One small clinical study shows that bitter orange juice slightly increases indinavir levels, but this effect is likely to be clinically insignificant. Bitter orange selectively inhibits intestinal cytochrome P450 3A4 (CYP3A4); however, the metabolism of indinavir seems to be more dependent on hepatic CYP3A4. The effect of bitter orange on other protease inhibitors has not been studied.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Bitter orange juice might increase blood levels of sildenafil.
A small clinical study in healthy adult males shows that drinking freshly squeezed bitter orange juice 250 mL daily for 3 days and taking a single dose of sildenafil 50 mg on the 3rd day increases the peak plasma concentration of sildenafil by 18% and the overall exposure to sildenafil by 44%. Theoretically, this may be due to inhibition of cytochrome P450 3A4 by bitter orange.

Likelihood Probable Evidence B
Stimulant Drugs

Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
Bitter orange appears to have stimulant effects.

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

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Bitter Orange full monograph & interactions

Peppermint5 drug types · 796 drugs

Cyclosporine (Neoral, Sandimmune)

Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.
In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction. An interaction between peppermint oil and cyclosporine has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP2C19 substrates.
In vitro research shows that peppermint oil inhibits CYP2C19. So far, this interaction has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP2C9 substrates.
In vitro research shows that peppermint oil inhibits CYP2C9. So far, this interaction has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP3A4 substrates.
Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate. However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations.

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

Theoretically, peppermint might increase the levels of CYP1A2 substrates.
In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2. However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference.

Likelihood Possible Evidence B
Peppermint full monograph & interactions

Tangerine2 drug types · 643 drugs

Cytochrome P450 3A4 (Cyp3A4) Substrates

In vitro, tangeretin, a constituent of tangerine, induces a 52% increase in the metabolism of midazolam by cytochrome P450 3A4 (CYP3A4). This suggests that tangeretin may stimulate CYP3A4 activity. However, in humans, drinking tangerine juice 200 mL slightly delayed the absorption, but did not affect the metabolism, of midazolam, a CYP3A4 substrate. Theoretically, tangerine juice might increase CYP3A4 activity and decrease levels of drugs metabolized by this enzyme. However, this effect is unlikely.
Some drugs metabolized by CYP3A4 include amitriptyline (Elavil), amiodarone (Cordarone), citalopram (Celexa), felodipine (Plendil), lansoprazole (Prevacid), ondansetron (Zofran), prednisone (Deltasone, Orasone), sertraline (Zoloft), sibutramine (Meridia), and many others.

Likelihood Unlikely Evidence B
Midazolam (Versed)

In vitro, tangeretin, a constituent of tangerine, appears to increase the metabolism of midazolam in human liver microsomes by up to 52%. However, in humans, drinking tangerine juice 200 mL slightly delayed the absorption, but did not affect the metabolism, of midazolam. Theoretically, tangerine juice might increase the metabolism and reduce the effects of midazolam. However, this effect is unlikely.

Likelihood Unlikely Evidence B
Tangerine full monograph & interactions

Kudzu7 drug types · 584 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, kudzu may increase the risk of bleeding if used with antiplatelet or anticoagulant drugs.
Kudzu isoflavones are reported to have antiplatelet activity.

Likelihood Possible Evidence D
Caffeine

Theoretically, taking kudzu with caffeine might increase levels of caffeine.
In healthy males injected with the kudzu constituent puerarin, caffeine clearance and metabolism is inhibited. This effect has been attributed to inhibition of cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if taking kudzu orally would have this same effect.

Likelihood Probable Evidence D
Estrogens

Theoretically, kudzu might alter the effects of estrogen therapy.
Some research suggests that kudzu has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.

Likelihood Possible Evidence B
Hepatotoxic Drugs

Theoretically, concomitant use might have additive hepatotoxic effects.
There is some concern that kudzu can adversely affect the liver.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, taking kudzu with methotrexate might increase the risk of methotrexate toxicity.
Preclinical research suggests that kudzu extract greatly reduces the elimination and increases the toxicity of methotrexate. Kudzu might inhibit organic anion transporters (OATs) that are responsible for hepatobiliary and renal excretion of anions, similar to the interaction between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs).

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, kudzu might interfere with tamoxifen activity.
Some research suggests that kudzu may have estrogenic effects.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking kudzu with antidiabetes drugs might increase the risk of hypoglycemia.
Kudzu might lower blood glucose levels and have additive effects in patients treated with antidiabetic agents. The dose of diabetes medications might need to be adjusted.

Likelihood Unlikely Evidence D
Kudzu full monograph & interactions

Poria Mushroom3 drug types · 417 drugs

Anticholinergic Drugs

Theoretically, poria mushroom might decrease the clinical effects of anticholinergic drugs.
In animal research, poria mushroom essential oil reduces acetylcholinesterase activity. This interaction has not been shown in humans.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, poria mushroom might have additive effects when used with cholinergic drugs.
In animal research, poria mushroom essential oil reduces acetylcholinesterase activity. This interaction has not been shown in humans.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, taking poria mushroom extract may enhance the therapeutic and adverse effects of sedatives.
Animal research shows that poria mushroom extract has sedative properties. This interaction has not been shown in humans.

Likelihood Possible Evidence D
Poria Mushroom full monograph & interactions

Burdock1 drug type · 122 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk of bleeding.

In vitro research shows that lignans from burdock reduce rabbit platelet aggregation by inhibiting platelet activating factor. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Burdock full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Cold-Zero, from the product label.

Nature's Health

See all Nature's Health products
Name
Nature's Health
City
Salt Lake City
State
UT
ZipCode
84115
Phone Number
(888) 270-0649
Web Address
www.natureshealth.com
Pharmacist Counseling Corner

Cold-Zero by Nature's Health: Common Questions

Does Cold-Zero by Nature's Health interact with any medications?
Yes. Based on its ingredients, Cold-Zero has a known interaction with 1,569 medications, including 10 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Cold-Zero contains 14 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is Cold-Zero safe during pregnancy or while breastfeeding?
No — several ingredients carry cautions. Burdock, Licorice, Kudzu, Costus, Perilla, and Poria Mushroom should be avoided in pregnancy and breastfeeding due to limited safety data or potential uterine effects. Bitter Orange is considered possibly unsafe in breastfeeding. Talk to your doctor or pharmacist about whether this product is right for you.
Does this actually help with a cold or cough?
We don't have evidence in our data showing these ingredients work for colds or cough. Peppermint and Licorice have some evidence for other conditions, but not cold symptoms. If you're looking for proven cold relief, ask your pharmacist what's been studied.
What are the most common side effects?
Most ingredients are well tolerated, but Licorice at high doses can cause headache, nausea, or vomiting, and may raise blood pressure over time. Peppermint can cause abdominal pain, diarrhea, or heartburn. Bitter Orange may raise blood pressure and heart rate, especially if combined with caffeine. If you notice any new symptoms, stop and contact your pharmacist.
Can I take this with my heart medication or blood thinner?
Maybe not — Licorice, Burdock, and Kudzu all interact with heart drugs and blood thinners at Moderate severity, and Bitter Orange poses additional risks. Check your exact medications with the tool on this page or ask your pharmacist before you start.
What is Bitter Orange, and why does it matter?
Bitter Orange (also called Seville orange) is a citrus fruit whose peel contains stimulant compounds like synephrine. It can raise blood pressure and heart rate, and it blocks liver enzymes that clear certain medications, making them accumulate. If you take sedatives, antidepressants, or heart drugs, Bitter Orange is a major concern.
Can I take this with caffeine or energy drinks?
Probably not safely. Bitter Orange combined with caffeine can significantly raise blood pressure and heart rate. Kudzu may also increase caffeine levels in your blood. If you're a regular caffeine user, talk to your pharmacist first.

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

Not sure if Cold-Zero is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.

Cold-Zero label
Go deeper

The Full Monographs Behind Cold-Zero’s Ingredients

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

Herb & supplement monograph

Burdock

Interacts with 122 drugs

Burdock is a traditional herb most often used for skin problems and as a so-called 'blood purifier,' but high-quality human studies are lacking and most claims are not well proven. It is wid...

Read the full Burdock 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

Peppermint

Interacts with 796 drugs

Peppermint is a popular herb with the best evidence supporting enteric-coated peppermint oil for easing IBS symptoms. It is generally well tolerated for most adults, but it can cause heartbu...

Read the full Peppermint monograph → Herb & supplement monograph

Costus

Costus (Saussurea costus) is a root used in Ayurvedic, Unani, and traditional Chinese medicine, mostly for digestive and respiratory complaints. High-quality human evidence is very limited,...

Read the full Costus monograph → Herb & supplement monograph

Tangerine

Interacts with 643 drugs

Tangerine is a sweet citrus fruit that is a good source of vitamin C and other nutrients, and is widely enjoyed as food. While the peel and essential oil are used in traditional medicine and...

Read the full Tangerine monograph → Herb & supplement monograph

Perilla

Perilla is an Asian mint-family plant used in cooking and traditional medicine, mainly for allergy, breathing, and digestive complaints. Most human evidence is limited or preliminary, so it...

Read the full Perilla monograph → Herb & supplement monograph

Japanese Mint

Japanese mint is a menthol-rich plant used mainly for its essential oil in topical rubs, inhalants, and digestive remedies. There is some support for menthol's soothing and cooling effects,...

Read the full Japanese Mint monograph → Herb & supplement monograph

Kudzu

Interacts with 584 drugs

Kudzu is a fast-growing vine whose root has long been used in traditional Chinese medicine and is now studied mostly for reducing alcohol intake. Early research is promising for cutting back...

Read the full Kudzu monograph → Herb & supplement monograph

Bitter Orange

Interacts with 957 drugs

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance i...

Read the full Bitter Orange monograph → Herb & supplement monograph

Poria Mushroom

Interacts with 417 drugs

Poria mushroom (Fu Ling) is a fungus long used in Traditional Chinese Medicine, mainly as a mild diuretic and digestive and calming aid. Modern scientific evidence in humans is very limited,...

Read the full Poria Mushroom monograph →
Sources

Sources & How We Checked

Cold-Zero'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 230 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.

Burdock 11 references
  1. Iwakami S, Wu JB, Ebizuka Y, Sankawa U. Platelet activating factor (PAF) antagonists contained in medicinal plants: lignans and sesquiterpenes. Chem Pharm Bull (Tokyo) 1992;40:1196-8. PubMed
  2. Sasaki Y, Kimura Y, Tsunoda T, Tagami H. Anaphylaxis due to burdock. Int J Dermatol 2003;42:472-3. PubMed
  3. Rhoads PM, Tong TG, Banner W Jr, Anderson R. Anticholinergic poisonings associated with commercial burdock root tea. J Toxicol Clin Toxicol 1984-85;22:581-4. PubMed
  4. Rodriguez P, Blanco J, Juste S, et al. Allergic contact dermatitis due to burdock (Arctium lappa). Contact Dermatitis 1995;33:134-5.
  5. Kassler, W. J., Blanc, P., and Greenblatt, R. The use of medicinal herbs by human immunodeficiency virus-infected patients. Arch Intern Med 1991;151(11):2281-2288. DOI
  6. Chan, Y. S., Cheng, L. N., Wu, J. H., Chan, E., Kwan, Y. W., Lee, S. M., Leung, G. P., Yu, P. H., and Chan, S. W. A review of the pharmacological effects of Arctium lappa (burdock). Inflammopharmacology. 2011;19(5):245-254. PubMed
  7. Breed, F. B. and Kuwabara, T. Burdock ophthalmia. Arch Ophthalmol 1966;75(1):16-20.
  8. Bryson, P. D., Watanabe, A. S., Rumack, B. H., and Murphy, R. C. Burdock root tea poisoning. Case report involving a commercial preparation. JAMA 5-19-1978;239(20):2157. DOI
  9. <p>Fletcher GF<span>, </span>Cantwell JD. Burdock root tea poisoning. JAMA <span>1978 Oct 6;240(15):1586.</span></p> DOI
  10. Latif A, Fichadiya H, Abid F, Capo G. Herbal Teas and Thrombocytopenia: A Curious Case of Yellow Dock and Burdock-Induced Thrombocytopenia. Eur J Case Rep Intern Med 2022;9(3):003247. PubMed
  11. Niazi B, Ahmed K, Ahmed M, Ali S, Song K, Elias S. Drug-Induced Liver Injury from Herbal Liver Detoxification Tea. Case Rep Gastroenterol 2022;16(3):612-617. PubMed

See these in context on the Burdock 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 →

Peppermint 41 references
  1. Liu JH, Chen GH, Yeh HZ, et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol 1997;32:765-8. PubMed
  2. Pittler MH, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am J Gastroenterol 1998;93:1131-5. PubMed
  3. Kline RM, Kline JJ, Di Palma J, Barbero GJ. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr 2001;138:125-8. PubMed
  4. Madisch A, Heydenreich CJ, Wieland V, et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled, double-blind equivalence study. Arzneimittel
  5. May B, Kuntz HD, Kieser M, Kohler S. Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia. Arzneimittelforschung 1996;46:1149-53.
  6. Micklefield GH, Greving I, May B. Effects of peppermint oil and caraway oil on gastroduodenal motility. Phytother Res 2000;14:20-3. DOI
  7. Morton CA, Garioch J, Todd P, et al. Contact sensitivity to menthol and peppermint in patients with intra-oral symptoms. Contact Dermatitis 1995;32:281-4. PubMed
  8. May B, Kohler S, Schneider B. Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment Pharmacol Ther 2000;14:1671-7. PubMed
  9. Nash P, Gould SR, Bernardo DE. Peppermint oil does not relieve the pain of irritable bowel syndrome. Br J Clin Pract 1986;40:292-3. DOI
  10. Rees WD, Evans BK, Rhodes J. Treating irritable bowel syndrome with peppermint oil. Br Med J 1979;2:835-6. PubMed
  11. Davies SJ, Harding LM, Baranowski AP. A novel treatment of postherpetic neuralgia using peppermint oil. Clin J Pain 2002;18:200-2. PubMed
  12. Weston CF. Anal burning and peppermint oil. Postgrad Med J 1987;63:717. PubMed
  13. Dresser GK, Wacher V, Wong S, et al. Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Clin Pharmacol Ther 2002;72:247-55. PubMed
  14. Wacher VJ, Wong S, Wong HT. Peppermint oil enhances cyclosporine oral bioavailability in rats: comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole. J Pharm Sci 2002;91:77-90.
  15. Lawson MJ, Knight RE, Tran K, et al. Failure of enteric-coated peppermint oil in the irritable bowel syndrome: a randomized double-blind crossover study. J Gastroenterol Hepatol 1988;3:235-8. DOI
  16. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  17. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  18. Rogers SN, Pahor AL. A form of stomatitis induced by excessive peppermint consumption. Dent Update 1995;22:36-7.
  19. Cappello G, Spezzaferro M, Grossi L, et al. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. Dig Liver Dis 2007;39:530-6. PubMed
  20. Moghadam BK, Gier R, and Thurlow T. Extensive oral mucosal ulcerations caused by misuse of a commercial mouthwash. Cutis 1999;64:131-134.
  21. Andersen, K. E. Contact allergy to toothpaste flavors. Contact Dermatitis 1978;4(4):195-198. PubMed
  22. Barnard, D. R. Repellency of essential oils to mosquitoes (Diptera: Culicidae). J Med Entomol. 1999;36(5):625-629. PubMed
  23. Tamir, S., Davidovich, Z., Attal, P., and Eliashar, R. Peppermint oil chemical burn. Otolaryngol.Head Neck Surg. 2005;133(5):801-802. PubMed
  24. Kalavala, M., Hughes, T. M., Goodwin, R. G., Anstey, A. V., and Stone, N. M. Allergic contact dermatitis to peppermint foot spray. Contact Dermatitis 2007;57(1):57-58. PubMed
  25. Vermaat, H., van Meurs, T., Rustemeyer, T., Bruynzeel, D. P., and Kirtschig, G. Vulval allergic contact dermatitis due to peppermint oil in herbal tea. Contact Dermatitis 2008;58(6):364-365. PubMed
  26. Merat, S., Khalili, S., Mostajabi, P., Ghorbani, A., Ansari, R., and Malekzadeh, R. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome. Dig.Dis.Sci. 2010;55(5):1385-1390. PubMed
  27. Tran, A., Pratt, M., and DeKoven, J. Acute allergic contact dermatitis of the lips from peppermint oil in a lip balm. Dermatitis 2010;21(2):111-115. DOI
  28. Hitz, Lindenmuller, I and Lambrecht, J. T. Oral care. Curr Probl.Dermatol 2011;40:107-115.
  29. Shavakhi, A., Ardestani, S. K., Taki, M., Goli, M., and Keshteli, A. H. Premedication with peppermint oil capsules in colonoscopy: a double blind placebo-controlled randomized trial study. Acta Gastroenterol Belg 2012;75(3):349-353.
  30. Lech, Y., Olesen, K. M., Hey, H., Rask-Pedersen, E., Vilien, M., and Ostergaard, O. [Treatment of irritable bowel syndrome with peppermint oil. A double- blind study with a placebo]. Ugeskr.Laeger 10-3-1988;150(40):2388-2389.
  31. Parys, B. T. Chemical burns resulting from contact with peppermint oil mar: a case report. Burns Incl.Therm.Inj. 1983;9(5):374-375. PubMed
  32. Bayat R, Borici-Mazi R. A case of anaphylaxis to peppermint. Allergy Asthma Clin Immunol. 2014;10(1):6. PubMed
  33. Rich G, Shah A, Koloski N, et al. A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil 2 PubMed
  34. Douros A, Bronder E, Andersohn F, et al. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study. Int J Mol Sci 2016;17(1). PubMed
  35. Begas E, Tsioutsiouliti A, Kouvaras E, et al. Effects of peppermint tea consumption on the activities of CYP1A2, CYP2A6, Xanthine Oxidase, N-acetyltranferase-2 and UDP-glucuronosyltransferases-1A1/1A6 in healthy volunteers. Food Chem Toxicol 2017;100:80-9 PubMed
  36. Cash BD, Epstein MS, Shah SM. A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms. Dig Dis Sci 2016;61(2):560-71. PubMed
  37. Elsaie LT, El Mohsen AM, Ibrahim IM, Mohey-Eddin MH, Elsaie ML. Effectiveness of topical peppermint oil on symptomatic treatment of chronic pruritus. Clin Cosmet Investig Dermatol 2016;9:333-8. PubMed
  38. Wu J, Xu R, Zhan R, et al. Effective symptomatic treatment for severe and intractable pruritus associated with severe burn-induced hypertrophic scars: A prospective, multicenter, controlled trial. Burns 2016;42(5):1059-66. PubMed
  39. Weerts ZZRM, Masclee AAM, Witteman BJM, et al. Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Gastroenterology. 2020;158(1):123-136. PubMed
  40. Nee J, Ballou S, Kelley JM, et al. Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial. Am J Gastroenterol 2021;116(11):2279-2285. PubMed
  41. Ingrosso MR, Ianiro G, Nee J, et al. Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome. Aliment Pharmacol Ther 2022;56(6):932-41. PubMed

See these in context on the Peppermint monograph →

Costus 6 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. Marzulli, F. N. and Maibach, H. I. Effects of vehicles and elicitation concentration in contact dermatitis testing. I. Experimental contact sensitization in humans. Contact Dermatitis 1976;2(6):325-329. PubMed
  3. Mitchell, J. C. Contact hypersensitivity to some perfume materials. Contact Dermatitis 1975;1(4):196-199. PubMed
  4. Benezra, C. and Epstein, W. L. Molecular recognition patterns of sesquiterpene lactones in costus-sensitive patients. Contact Dermatitis 1986;15(4):223-230. PubMed
  5. Mitchell, J. C. and Epstein, W. L. Contact hypersensitivity to a perfume material, Costus Absolute. The role of sesquiterpene lactones. Arch.Dermatol 1974;110(6):871-873. DOI
  6. Cheminat, A., Stampf, J. L., Benezra, C., Farrall, M. J., and Frechet, J. M. Allergic contact dermatitis to costus: removal of haptens with polymers. Acta Derm.Venereol. 1981;61(6):525-529. DOI

See these in context on the Costus monograph →

Tangerine 3 references
  1. Yuan, J. M., Wang, X. L., Xiang, Y. B., Gao, Y. T., Ross, R. K., and Yu, M. C. Preserved foods in relation to risk of nasopharyngeal carcinoma in Shanghai, China. Int J Cancer 2000;85(3):358-363. DOI
  2. Backman, J. T., Maenpaa, J., Belle, D. J., Wrighton, S. A., Kivisto, K. T., and Neuvonen, P. J. Lack of correlation between in vitro and in vivo studies on the effects of tangeretin and tangerine juice on midazolam hydroxylation. Clin Pharmacol Ther 2000; PubMed
  3. Vilaplana, J. and Romaguera, C. Contact dermatitis from the essential oil of tangerine in fragrance. Contact Dermatitis 2002;46(2):108. PubMed

See these in context on the Tangerine monograph →

Perilla 4 references
  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Kanzaki, T. and Kimura, S. Occupational allergic contact dermatitis from Perilla frutescens (shiso). Contact Dermatitis 1992;26(1):55-56.
  3. Yu H, Qiu JF, Ma LJ, Hu YJ, Li P, Wan JB. Phytochemical and phytopharmacological review of Perilla frutescens L. (Labiatae), a traditional edible-medicinal herb in China. Food Chem Toxicol 2017;108(Pt B):375-91. PubMed
  4. Jeong K, Lee SY, Jeon SA, et al. Clinical and immunological characterization of perilla seed allergy in children. J Investig Allergol Clin Immunol 2021. PubMed

See these in context on the Perilla monograph →

Japanese Mint 2 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. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

See these in context on the Japanese Mint monograph →

Kudzu 21 references
  1. Woo J, Lau E, Ho SC, et al. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Menopause 2003;10:352-61. PubMed
  2. Akita H, Sowa J, Makiura M, et al. Maculopapular drug eruption due to the Japanese herbal medicine Kakkonto (kudzu or arrowroot decoction). Contact Dermatitis 2003;48:348-9. PubMed
  3. Luo ZR, Zheng B. [Effect of Puerarin on platelet activating factors CD63 and CD62P, plasminogen activator inhibitor and C-reactive protein in patients with unstable angia pectoris]. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001;21:31-3 .
  4. Lee KT, Sohn IC, Kim DH, et al. Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-lnduced diabetic rat and their antioxidant activity in vitro. Arch Pharm Res 2000;23:461-6.
  5. Yu Z, Zhang G, Zhao H. [Effects of Puerariae isoflavone on blood viscosity, thrombosis and platelet function]. Zhong Yao Cai 1997;20:468-9.
  6. Hsu FL, Liu IM, Kuo DH, et al. Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod 2003;66:788-92. PubMed
  7. Chiang HM, Fang SH, Wen KC, et al. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. Toxicol Appl Pharmacol 2005;209:263-8.
  8. Zheng, J., Chen, B., Jiang, B., Zeng, L., Tang, Z. R., Fan, L., and Zhou, H. H. The effects of puerarin on CYP2D6 and CYP1A2 activities in vivo. Arch Pharm Res 2010;33(2):243-246. PubMed
  9. Hsu, H. H., Chang, C. K., Su, H. C., Liu, I. M., and Cheng, J. T. Stimulatory effect of puerarin on alpha1A-adrenoceptor to increase glucose uptake into cultured C2C12 cells of mice. Planta Med 2002;68(11):999-1003.
  10. Zheng, G., Zhang, X., Zheng, J., Meng, Q., and Zheng, D. [Estrogen-like effects of puerarin and total isoflavones from Pueraria lobata]. Zhong.Yao Cai. 2002;25(8):566-568.
  11. Qi, B. L. and Qi, B. M. [Effect of the purariae-isofiavones on estrogen level in normal and ovariectomized rats]. Zhongguo Zhong.Yao Za Zhi. 2002;27(11):850-852.
  12. Akita, H., Sowa, J., Makiura, M., Akamatsu, H., and Matsunaga, K. Maculopapular drug eruption due to the Japanese herbal medicine Kakkonto (kudzu or arrowroot decoction). Contact Dermatitis 2003;48(6):348-349. PubMed
  13. Manonai, J., Chittacharoen, A., Theppisai, U., and Theppisai, H. Effect of Pueraria mirifica on vaginal health. Menopause. 2007;14(5):919-924. PubMed
  14. Chandeying, V. and Sangthawan, M. Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study. J M
  15. Virojchaiwong, P., Suvithayasiri, V., and Itharat, A. Comparison of Pueraria mirifica 25 and 50 mg for menopausal symptoms. Arch.Gynecol.Obstet. 2011;284(2):411-419. PubMed
  16. Hou, Q., Ao, X., Li, G., and Zhang, Y. [Puerarin combined with avandia for diabetic nephropathy]. Zhong.Nan.Da.Xue Xue Bao Yi Xue Ban. 2012;37(1):73-77.
  17. Kim HJ, Kim H, Ahn JH, Suk JH. Liver injury induced by herbal extracts containing mistletoe and kudzu. J Altern Complement Med 2015;21(3):180-5. PubMed
  18. Santosh N, Mohan K, Royana S, Yamini TB. Hepatotoxicity of tubers of Indian Kudzu (Pueraria tuberosa) in rats. Food Chem Toxicol. 2010 Apr;48(4):1066-71. PubMed
  19. Teschke R, Zhang L, Long H, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, Wolff A, Frenzel C, Schulze J, Eickhoff A. Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases. Ann Hepatol. 2015 Jan-Feb;14(1):7-19. DOI
  20. Wang D, Qiu L, Wu X, Wei H, Xu F. Evaluation of kudzu root extract-induced hepatotoxicity. J Ethnopharmacol. 2015 Dec 24;176:321-6. PubMed
  21. Warinsiriruk P, Tantitham C, Cherdshewasart W, Shobeiri SA, Manonai J. Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause. Maturitas 2022;160:4-10. PubMed

See these in context on the Kudzu monograph →

Bitter Orange 47 references
  1. Penzak SR, Jann MW, Cold JA, et al. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J Clin Pharmacol 2001;41:1059-63. PubMed
  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. Calapai G, Firenzuoli F, Saitta A, et al. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: A preliminary report. Fitoterapia 1999;70:586-92. DOI
  4. Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J 1985;291:940.
  5. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001;69:14-23. PubMed
  6. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  7. Colker CM, Kalman DS, Torina GC, et al. Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  8. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70. PubMed
  9. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  10. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  11. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  12. Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38:812-6. PubMed
  13. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: Current status of clinical and basic Research. Exp Biol Med 2004;229:698-704.
  14. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. PubMed
  15. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed
  16. Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12:247-8. PubMed
  17. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc 2005;80:541-5. PubMed
  18. Haller CA, Benowitz NL, Jacob P 3rd. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118:998-1003.. PubMed
  19. Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 2006;40:53-7. PubMed
  20. Min B, Cios D, Kluger J, White CM. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy 2005;25:1719-24. PubMed
  21. Gange CA, Madias C, Felix-Getzik EM, et al. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc 2006;81:545-8. PubMed
  22. Jordan S, Murty M, Pilon K. Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. Canadian Adverse Reaction Newsletter 2004;14:3-4.
  23. Burke J, Seda G, Allen D, Knee TS. A case of severe exercise-induced rhabdomyolysis associated with a weight loss dietary supplement. Mil Med 2007;172:656-8. PubMed
  24. Gray, S. and Woolf, A. D. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J Adolesc.Health 2005;37(5):414-415. PubMed
  25. Haller, C. A., Duan, M., Jacob, P., III, and Benowitz, N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br J Clin Pharmacol 2008;65(6):833-840. PubMed
  26. Thomas, J. E., Munir, J. A., McIntyre, P. Z., and Ferguson, M. A. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex.Heart Inst.J 2009;36(6):586-590.
  27. Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic ef
  28. Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., and Stohs, S. J. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci 2011;8(3):192-197. PubMed
  29. Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., and Kaats, G. R. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med
  30. Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173. PubMed
  31. Kaats, G. R., Miller, H., Preuss, H. G., and Stohs, S. J. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.
  32. Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F. R., Arlotta, M., Costantino, G., and Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 12-1-1999;70(6):586-592. DOI
  33. Colker, C., Kalman, D., and Torina, G. Effects of Citrus aurantium extract, caffeine, and St. John's Wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res 1999;60:145-153. DOI
  34. Shara M, Stohs SJ. Safety evaluation of Bitter orange extract (p-synephrine) in healthy volunteers. J.Amer.Coll.Nutr. 2011;30:358.
  35. Lynch B. Review of the safety of p-synephrine and caffeine. Intertek-Cantox Report, 2013;1-20.
  36. Smith TB, Staub BA, Natarajan GM, et al. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. Tex Heart Inst J 2014;41(1):70-2. PubMed
  37. Shara M, Stohs SJ, Mukattash TL. Cardiovascular safety of oral p-synephrine (bitter orange) in healthy subjects: a randomized placebo-controlled cross-over clinical trial. Phytother Res. 2016;30(5):842-7.
  38. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
  39. Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. Drugs R D. 2016 Sep;16(3):271-278. PubMed
  40. Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, et al. Acute consumption of p-synephrine does not enhance performance in sprint athletes.J. Appl Physiol Nutr Metab. 2016;41(1):63-9. doi: 10.1139/apnm-2015-0299.
  41. Jung YP, Earnest CP, Koozehchian M, et al. Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2017;3;14:1. doi: 10.1186/s12970-016-0158- PubMed
  42. Jung YP, Earnest CP, Koozehchian M, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr. 2017;14:3. doi: 10.118
  43. Vatsavai LK, Kilari EK. Interaction of p-synephrine on the pharmacodynamic and pharmacokinetics of gliclazide in animal models. J Ayurveda Integr Med 2017; S0975-9476(16)30487-9. doi: 10.1016/j.jaim.2017.04.010.
  44. Ratamess NA, Bush JA, Stohs SJ, et al. Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study. Phytother Res. 2018;32(1):94-102.
  45. Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso J. Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax. Eur J Nutr. 2019 Nov 5. PubMed
  46. Karimzadeh Z, Azizzadeh Forouzi M, Tajadini H, Ahmadinejad M, Roy C, Dehghan M. Effects of lavender and Citrus aurantium on pain of conscious intensive care unit patients: a parallel randomized placebo-controlled trial. J Integr Med 2021:S2095-4964(21)000 PubMed
  47. Koncz D, Tóth B, Bahar MA, Roza O, Csupor D. The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis. Nutrients 2022;14(19):4019. PubMed

See these in context on the Bitter Orange monograph →

Poria Mushroom 3 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Kim H, Park I, Park K, Park S, Kim YI, Park BG. The positive effects of Poria cocos extract on quality of sleep in insomnia rat models. Int J Environ Res Public Health 2022;19(11):6629. PubMed
  3. Lv Q, Di X, Bian B, Li K, Guo J. Neuroprotective effects of Poria cocos (Agaricomycetes) essential oil on Aß1-40-induced learning and memory deficit in rats. Int J Med Mushrooms 2022;24(10):73-82.

See these in context on the Poria Mushroom monograph →

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

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