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

Seasonal Defense Ingredients & Drug Interactions

by Nature's Sunshine

Seasonal Defense 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 Seasonal Defense 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

Seasonal Defense is a dietary supplement by Nature's Sunshine with 5 active ingredients. Its ingredients are commonly taken for fatigue and low energy, physical and athletic performance, stress resistance (adaptogen).Based on those ingredients, 1,458 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Eleuthero, Bitter Orange Fruit, Andrographis paniculata whole plant extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Seasonal Defense by Nature's Sunshine

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

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Seasonal Defense by Nature's Sunshine

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 Sep 10, 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 5 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (470 mg) without saying how much of each component you get.

Seasonal Defense contains five active ingredients: eleuthero, oregano, andrographis paniculata (whole plant extract), thyme, and bitter orange fruit, all delivered in capsule form. Eleuthero is included as an adaptogenic herb traditionally used to support energy and resilience.

Oregano, andrographis, and thyme are antimicrobial and antioxidant herbs often chosen for seasonal wellness support. Bitter orange fruit is added for its stimulant properties.

The product also contains inactive ingredients (magnesium stearate, silicon dioxide, gelatin, and water) as binders and capsule material.

Does it work?

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

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

Why this rating?
  • The label markets this product for: immune system support during seasonal changes.
  • We looked for evidence on: Common cold, Influenza, Cough, Acute bronchitis, Bronchitis, Laryngitis — and 4 related terms.
  • The closest evidence on file: Oregano is rated "Insufficient Reliable Evidence To Rate" for Bronchitis (Natural Medicines).
  • Also on file: Oregano is rated "Insufficient Reliable Evidence To Rate" for Cough.
  • Also on file: Thyme is rated "Insufficient Reliable Evidence To Rate" for Bronchitis, Common cold, Cough, Laryngitis.

The evidence for Seasonal Defense's ingredients is mixed and often limited. Eleuthero is rated possibly effective for genital herpes, but evidence for its use in other conditions—chronic fatigue, bipolar disorder, osteoporosis, and familial Mediterranean fever—is insufficient.

Andrographis shows possibly effective evidence for ulcerative colitis, tonsillopharyngitis (throat inflammation), and osteoarthritis, but not for familial Mediterranean fever. Oregano, thyme, and bitter orange lack sufficient evidence in our data to support claims for acne, bronchitis, asthma, headache, upper respiratory infection, aging skin, alopecia, common cold, hay fever, sexual dysfunction, anxiety, or athletic performance.

If a particular condition is your reason for considering this product, check those ingredient ratings against your goal.

The evidence, ingredient by ingredient Eleuthero Oregano Andrographis Thyme Bitter Orange

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 5 of the 5 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 5 of 5.
  • General safety write-ups exist for 5 of 5.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Eleuthero is generally well tolerated for short-term use, though evidence on long-term safety is limited; it's best avoided during pregnancy and breastfeeding. Oregano is safe in food amounts but less studied in concentrated supplements; supplement amounts should be avoided during pregnancy, and breastfeeding safety isn't established.

Andrographis is generally well tolerated short-term but should be avoided during pregnancy due to theoretical reproductive concerns and during breastfeeding due to insufficient safety data. Thyme is likely safe in food and medicinal amounts during pregnancy and breastfeeding but concentrated essential oil should be avoided.

Bitter orange should not be used in supplement amounts during pregnancy or breastfeeding due to stimulant effects and lack of safety data. Common side effects across these ingredients include gastrointestinal upset, headache, nausea, and dizziness.

Eleuthero may cause nervousness, anxiety, or irritability, especially at higher doses. Oregano and andrographis can rarely cause severe allergic reactions, including anaphylaxis.

Bitter orange carries cardiovascular risks (high blood pressure, rapid heartbeat) particularly when combined with caffeine or other stimulants, and in rare cases has been linked to heart attack, stroke, and abnormal heart rhythms.

Side effects, ingredient by ingredient Eleuthero Oregano Andrographis Thyme Bitter Orange

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?
  • 5 of the 5 matched ingredients can interact with medications — Oregano, Thyme, Andrographis, Bitter Orange, Eleuthero.
  • 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: 1,459 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 Seasonal Defense, double-check the following medication types with your doctor or pharmacist, starting with the most serious: monoamine oxidase inhibitors (MAOIs) for depression, and midazolam or other sedatives. Also clear it with your doctor if you take blood thinners (anticoagulants) or antiplatelet drugs, any heart or blood-pressure medications (especially QT-prolonging drugs), antidiabetes drugs, immunosuppressants, stimulants, caffeine supplements, dextromethorphan (cough suppressant), heartbeat regulators like digoxin, estrogen therapy, anticholinergic or cholinergic drugs, pain relievers (etoricoxib or celecoxib), or any drug metabolized by the liver (CYP1A2, CYP2C9, CYP2D6, or CYP3A4 substrates).

No interactions are documented for the proprietary blend itself, but we hold no separate safety data for it.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with no established evidence rating for its marketed use. Major medication interactions have been identified, and safety information is well characterized.

Seasonal Defense may appeal to people seeking herbal support for seasonal wellness, though evidence for most of its uses is limited or insufficient. Because this product interacts with a large number of medications—including blood thinners, heart drugs, diabetes medications, and antidepressants—you'll want to check every prescription, over-the-counter drug, and other supplement you take against our search tool before starting.

Pregnant and breastfeeding individuals should avoid this product. Discuss it with your own doctor or pharmacist to confirm it's appropriate for your health situation and medications.

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

Assessment coverage: 5 of 5 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 1, 2012.

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 Seasonal Defense, straight from the product label.

Brand Nature's Sunshine
Net contents 90 Capsule(s)
Market status On market
Date entered into DSLD Oct 1, 2012
DSLD ID 13735
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), Kosher, 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 Seasonal Defense by Nature's Sunshine, 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:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
IngredientAmount% DV
Proprietary Blend470 mg--
Eleuthero0 NP--
Oregano0 NP--
Andrographis paniculata whole plant extract0 NP--
Thyme0 NP--
Bitter Orange Fruit0 NP--

Other ingredients: Magnesium Stearate, Silicon Dioxide, Gelatin, Water

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

Other Information: GUARANTEED PURE Immune System Support -Helps the Body Maintain Optimal Health During Seasonal Health Changes -Andrographis Specifically Helps Boost the Immune System, Minimizing the Duration of Seasonal Health Changes -This Unique Formulation Helps Support Mucous Membranes*

This is a unique combination of herbal ingredients that help the body maintain optimal health during seasonal changes. Andrographis paniculata is an immune and respiratory-supporting agent backed with scientific documentation that helps minimize the length and severity of seasonal health changes.*

Product of U.S.A.

Nature's Sunshine uses natural source materials in its products that are subject to color variation.

Seasonal Defense (90 caps)

Seals/Symbols

Ko

Nature's Sunshine QUALITY, SERVICE INTEGRITY(R)

FDA Disclaimer Statement

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

Precautions

This bottle was sealed for your protection. Do not use if inner seal is missing or damaged.

Warning: NOTICE: Pregnant or lactating women should consult their health-care provider prior to taking this supplement.

FDA Statement of Identity

Description: Herbal Combination Supplement-480 mg each

Suggested/Recommended/Usage/Directions

Recommended Usage: Take one capsule with a meal three times daily.

Brand IP Statement(s)

Nature's Sunshine(R) United States

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

See for yourself

Seasonal Defense by Nature's Sunshine label

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

Seasonal Defense 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 Seasonal Defense by Nature's Sunshine

These are the 5 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule 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

470 mg per serving

Other (inactive) ingredients: Magnesium Stearate, Silicon Dioxide, Gelatin, Water. These complete the product’s ingredient list but are not active constituents.

Interaction report

Seasonal Defense by Nature's Sunshine Drug Interactions

Want to check YOUR meds against Seasonal Defense?

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
1,458Drugs
10 Major 1,407 Moderate 41 Minor

Ingredients driving the most interactions

Eleuthero 1,140
Bitter Orange Fruit 957
Andrographis paniculata whole plant extract 413
Thyme 379
Oregano 208

Individual Drug Interactions

The ingredients in Seasonal Defense interact with 1,458 drugs. Click any drug to see the details.

5 of the 5 ingredients in Seasonal Defense interact with drugs. Each result below shows which ingredient is responsible. Eleuthero Bitter Orange Fruit Andrographis paniculata whole plant extract Thyme Oregano

Each ingredient & the kinds of drugs it affects

For each ingredient in Seasonal Defense 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.

Eleuthero10 drug types · 1,140 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals. A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels. However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo. These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9. This effect has not been reported in humans.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Eleuthero might increase serum digoxin levels and increase the risk of side effects.
In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal. It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay. Although the product was found to be free of digoxin and digitoxin, it was not tested for other contaminants.

Likelihood Unlikely Evidence D
Immunosuppressants

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.

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

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1. Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

Likelihood Possible Evidence D
Eleuthero full monograph & interactions

Bitter Orange Fruit13 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 Fruit full monograph & interactions

Andrographis paniculata whole plant extract6 drug types · 413 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, andrographis might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Animal and laboratory studies suggest that andrographis has antiplatelet effects.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, andrographis might increase the risk of hypotension when used with antihypertensive drugs.
Animal research suggests that andrographis has hypotensive effects.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, andrographis might interfere with the effects of immunosuppressive drugs.
Laboratory research suggests that andrographolide has immunostimulant activity.

Likelihood Possible Evidence D
Celecoxib (Celebrex)

Theoretically, andrographis extract might increase the maximum concentration and time to peak concentration of celecoxib. The clinical significance of these changes is unclear.
Animal research suggests that andrographis extract taken orally increases the maximum concentration and time to peak concentration of celecoxib but does not appear to impact the area under the curve.

Likelihood Possible Evidence D
Etoricoxib (Arcoxia)

Theoretically, andrographis might decrease the absorption of etoricoxib, although the clinical significance is unclear.
Animal research shows that andrographis extract, or the constituent andrographolide, taken orally with etoricoxib decreases the bioavailability of etoricoxib. However, this reduced bioavailability is not correlated with a reduction in the anti-inflammatory effects of etoricoxib in arthritic mice models. The clinical significance of this interaction is unclear.

Likelihood Possible Evidence D
Glipizide (Glucotrol)

Theoretically, andrographis extract might increase the maximum concentration and area under the curve of glipizide; however, opposite effects are seen with the constituent, andrographolide. The clinical significance of this interaction is unclear.
Animal research suggests that andrographis extract taken orally with glipizide in diabetes-induced rats increases the maximum concentration and area under the curve of glipizide. However, the opposite effect is seen with the constituent, andrographolide, in which the maximum concentration and area under the curve are decreased when taken with glipizide.

Likelihood Possible Evidence D
Andrographis paniculata whole plant extract full monograph & interactions

Thyme4 drug types · 379 drugs

Anticholinergic Drugs

Theoretically, concurrent use of anticholinergic drugs and thyme essential oil might reduce the effects of anticholinergic drugs.
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE). However, this effect has not been observed in humans.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, thyme leaf extract might have additive effects with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that thyme leaf extract has antiplatelet effects. However, this effect has not been observed in humans.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of cholinergic drugs and thyme essential oil might cause additive cholinergic effects.
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE). However, this effect has not been observed in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, thyme might competitively inhibit the effects of estrogen replacement therapy.
In vitro research shows that thyme has estrogen receptor-binding activity and phytoestrogen content. However, this effect has not been observed in humans.

Likelihood Possible Evidence D
Thyme full monograph & interactions

Oregano2 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, oregano might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro research shows that aristolochic acid isolated from oregano leaves has antithrombin activity. It has also been reported that oregano oil inhibits arachidonic acid-induced, and ADP-induced, platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, oregano might increase the risk for hypoglycemia when taken with antidiabetes drugs.
In vitro and animal research shows that oregano extracts might lower blood glucose levels.

Likelihood Possible Evidence D
Oregano full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Seasonal Defense, from the product label.

Nature's Sunshine

See all Nature's Sunshine products
Name
Nature's Sunshine Products, Inc.
Pharmacist Counseling Corner

Seasonal Defense by Nature's Sunshine: Common Questions

Does Seasonal Defense by Nature's Sunshine interact with any medications?
Yes. Based on its ingredients, Seasonal Defense has a known interaction with 1,458 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?
Seasonal Defense contains 5 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 Seasonal Defense if I'm pregnant or breastfeeding?
No. Eleuthero, andrographis, and bitter orange should all be avoided during pregnancy due to insufficient safety data or theoretical reproductive concerns. Oregano in medicinal amounts and bitter orange in supplement amounts should also be avoided during pregnancy. For breastfeeding, eleuthero, andrographis, and bitter orange are not recommended due to lack of safety information, and oregano supplement safety isn't established. Talk with your doctor or pharmacist about safer options.
Does this product really help with colds and seasonal illness?
The evidence in our data is insufficient for most of the conditions these herbs are traditionally used for—including upper respiratory infection, bronchitis, common cold, and hay fever. Andrographis does show possibly effective evidence for tonsillopharyngitis (sore throat), but the other ingredients lack established proof of benefit for cold-season wellness.
What are the most common side effects?
The most common side effects are gastrointestinal upset, headache, nausea, and dizziness. Eleuthero may also cause nervousness or anxiety, especially at higher doses. Oregano and andrographis can cause rash or allergic reactions in some people. Bitter orange, particularly if combined with caffeine, can raise blood pressure and heart rate.
Is Seasonal Defense safe to use long-term?
Long-term safety is not well established. Eleuthero and andrographis are generally well tolerated short-term, but evidence for prolonged use is limited. Concentrated oregano oil is less studied than food amounts. If you're considering taking this for several months, check with your doctor or pharmacist first.
Why does this product have so many medication interactions?
Bitter orange is the main driver—it contains stimulant compounds that inhibit liver enzymes and interact with many medications, including MAOIs and sedatives. Eleuthero and andrographis also affect how your liver processes certain drugs. Even though most of these interactions are theoretical (shown in lab studies but not yet reported in people), they matter if you take any of the affected medications.
Can I take this with caffeine or energy drinks?
No. Bitter orange combined with caffeine can significantly raise blood pressure and heart rate and theoretically increase the risk of serious heart problems. If you consume caffeine regularly, avoid this product.

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

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

Seasonal Defense label
Go deeper

The Full Monographs Behind Seasonal Defense’s Ingredients

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

Herb & supplement monograph

Eleuthero

Interacts with 1,140 drugs

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence behind these uses is limited and mixed, so...

Read the full Eleuthero monograph → Herb & supplement monograph

Oregano

Interacts with 208 drugs

Oregano is a common Mediterranean cooking herb that is also sold as a concentrated oil or supplement, often standardized for a compound called carvacrol. While lab studies suggest it may hav...

Read the full Oregano monograph → Herb & supplement monograph

Andrographis

Interacts with 413 drugs

Andrographis is a bitter Asian herb traditionally used for colds, flu, and infections, and some studies suggest it may ease cold symptoms and shorten how long they last. The evidence is limi...

Read the full Andrographis monograph → Herb & supplement monograph

Thyme

Interacts with 379 drugs

Thyme is a common kitchen herb that has long been used for coughs, sore throats, and digestive complaints. It is generally safe in the amounts found in food, and some cough products that com...

Read the full Thyme 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 →
Sources

Sources & How We Checked

Seasonal Defense'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 127 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.

Eleuthero 24 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. McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ 1996;155:293-5.
  3. Awang DVC. Siberian ginseng toxicity may be case of mistaken identity (letter). CMAJ 1996;155:1237.
  4. Mills S, Bone K. Principles and Practice of Phytotherapy. London: Churchill Livingstone, 2000.
  5. Harkey MR, Henderson GL, Zhou L, et al. Effects of Siberian ginseng (Eleutherococcus senticosus) on c-DNA-expressed P450 drug metabolizing enzymes. Alt Ther 2001;7:S14.
  6. Hikino H, Takahashi M, Otake K, Konno C. Isolation and hypoglycemic activity of eleutherans A, B, C, D, E, F, and G: glycans of Eleutherococcus senticosus roots. J Nat Prod 1986;49:293-7. PubMed
  7. Yun-Choi HS, Kim JH, Lee JR. Potential inhibitors of platelet aggregation from plant sources, III. J Nat Prod 1987;50:1059-64. PubMed
  8. Donovan JL, DeVane CL, Chavin KD, et al. Siberian Ginseng (Eleutheroccus senticosus) Effects on CYP2D6 and CYP3A4 Activity in Normal Volunteers. Drug Metab Dispos 2003;31:519-22.. PubMed
  9. Hartz AJ, Bentler S, Noyes R et al. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med 2004;34:51-61. PubMed
  10. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. J Am Coll Nutr 2004;23:248-58. PubMed
  11. Dasgupta A, Wu S, Actor J, et al. Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Significant variation in digoxin-like immunoreactivity among commercial ginsengs. Am J Clin Pathol 2003;119:298-303. DOI
  12. Takahashi T, Kaku T, Sato T, et al. Effects of Acanthopanax senticosus HARMS extract on drug transport in human intestinal cell line Caco-2. J Nat Med. 2010;64(1):55-62. PubMed
  13. Fuchikami H, Satoh H, Tsujimoto M, Ohdo S, Ohtani H, Sawada Y. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006;34:577-82. PubMed
  14. Friedman, J. A., Taylor, S. A., McDermott, W., and Alikhani, P. Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins. Neurocrit.Care 2007;7(1):76-80. PubMed
  15. Molokovskii, D. S., Davydov, V. V., and Tiulenev, V. V. [The action of adaptogenic plant preparations in experimental alloxan diabetes]. Probl.Endokrinol.(Mosk) 1989;35(6):82-87.
  16. Schmolz, M. W., Sacher, F., and Aicher, B. The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots. Phytother.Res 2001;15(3):268-270.
  17. Huang, D. B., Ran, R. Z., and Yu, Z. F. [Effect of Acanthopanax senticosus injection on the activities of human tumor necrosis factor and natural killer cell in blood in the patients with lung cancer]. Zhongguo Zhong.Yao Za Zhi. 2005;30(8):621-624.
  18. Niu, H. S., Hsu, F. L., Liu, I. M., and Cheng, J. T. Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats. Horm.Metab Res 2007;39(12):894-898
  19. Watanabe, K., Kamata, K., Sato, J., and Takahashi, T. Fundamental studies on the inhibitory action of Acanthopanax senticosus Harms on glucose absorption. J Ethnopharmacol. 10-28-2010;132(1):193-199. PubMed
  20. Bazaz'ian, G. G., Liapina, L. A., Pastorova, V. E., and Zvereva, E. G. [Effect of Eleutherococcus on the functional status of the anticoagulation system in older animals]. Fiziol.Zh.SSSR Im I.M.Sechenova 1987;73(10):1390-1395.
  21. Kaloeva, Z. D. [Effect of the glycosides of Eleutherococcus senticosus on the hemodynamic indices of children with hypotensive states]. Farmakol.Toksikol. 1986;49(5):73.
  22. Martinez, B. and Staba, E. J. The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. Jpn J Pharmacol 1984;35(2):79-85. DOI
  23. Medon, P. J., Thompson, E. B., and Farnsworth, N. R. Hypoglycemic effect and toxicity of Eleutherococcus senticosus following acute and chronic administration in mice. Zhongguo Yao Li Xue.Bao. 1981;2(4):281-285.
  24. Freye E, GLeske J. Siberian ginseng results in beneficial effects on glucose metabolism in diabetes type 2 patients: a double blind placebo-controlled study in comparison to panax ginseng. Int J Clin Nutr. 2013;1(1):11-17.

See these in context on the Eleuthero monograph →

Oregano 12 references
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  2. Benito M, Jorro G, Morales C, et al. Labiatae allergy: systemic reactions due to ingestion of oregano and thyme. Ann Allergy Asthma Immunol 1996;76:416-8. PubMed
  3. Chevallier A. Encyclopedia of Herbal Medicine. 2nd ed. New York, NY: DK Publ, Inc., 2000.
  4. Ciganda C, and Laborde A. Herbal infusions used for induced abortion. J Toxicol.Clin Toxicol. 2003;41:235-239. PubMed
  5. Futrell, J. M. and Rietschel, R. L. Spice allergy evaluated by results of patch tests. Cutis 1993;52(5):288-290.
  6. 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
  7. Goun, E., Cunningham, G., Solodnikov, S., Krasnykch, O., and Miles, H. Antithrombin activity of some constituents from Origanum vulgare. Fitoterapia 2002;73(7-8):692-694. PubMed
  8. Lemhadri, A., Zeggwagh, N. A., Maghrani, M., Jouad, H., and Eddouks, M. Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region. J Ethnopharmacol. 2004;92(2-3):251-256. PubMed
  9. McCue, P., Vattem, D., and Shetty, K. Inhibitory effect of clonal oregano extracts against porcine pancreatic amylase in vitro. Asia Pac.J Clin.Nutr. 2004;13(4):401-408.
  10. Ragi, J., Pappert, A., Rao, B., Havkin-Frenkel, D., and Milgraum, S. Oregano extract ointment for wound healing: a randomized, double-blind, petrolatum-controlled study evaluating efficacy. J.Drugs Dermatol. 2011;10(10):1168-1172.
  11. Singletary K. Oregano: overview of the literature on health benefits. Nutrition Today 2010;45(3):129-38.
  12. Silva MLAE, Lucarini R, Dos Santos FF, et al. Hypoglycemic effect of rosmarinic acid-rich infusion (RosCE) from Origanum vulgare in alloxan-induced diabetic rats. Nat Prod Res 2022;36(17):4525-4531.

See these in context on the Oregano monograph →

Andrographis 26 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. Thamlikitkul V, Dechatiwongse T, Theerapong S, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai 1991;74:437-42.
  3. Zhang CY, Tan BK. Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat. J Ethnopharmacol 1997;56:97-101. PubMed
  4. Zhao HY, Fang WY. Antithrombotic effects of Andrographis paniculata nees in preventing myocardial infarction. Chin Med J (Engl) 1991;104:770-5.
  5. Amroyan E, Gabrielian E, Panossian A, et al. Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine 1999;6:27-31. PubMed
  6. Zhang C, Kuroyangi M, Tan BK. Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria. Pharmacol Res 1998;38:413-7. PubMed
  7. Puri A, Saxena R, Saxena RP, et al. Immunostimulant agents from Andrographis paniculata. J Nat Prod 1993;56:995-9. PubMed
  8. Melchoir J, Spasov AA, Ostrovskij OV, et al. Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan Jang) in the treatment of uncomplicated upper-respirator
  9. Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res 2000;14:333-8. PubMed
  10. Gabrielian ES, Shukarian AK, Goukasova GI, et al. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine 2002;9:589-97 PubMed
  11. Poolsup N, Suthisisang C, Prathanturarug S, et al. Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials. J Clin Pharm Ther 2004;29:37-45. PubMed
  12. Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med 2004;70:293-8.
  13. Kligler, B., Ulbricht, C., Basch, E., Kirkwood, C. D., Abrams, T. R., Miranda, M., Singh Khalsa, K. P., Giles, M., Boon, H., and Woods, J. Andrographis paniculata for the treatment of upper respiratory infection: a systematic review by the natural standa
  14. Burgos, R. A., Hancke, J. L., Bertoglio, J. C., Aguirre, V., Arriagada, S., Calvo, M., and Caceres, D. D. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled tria
  15. Saxena, R. C., Singh, R., Kumar, P., Yadav, S. C., Negi, M. P., Saxena, V. S., Joshua, A. J., Vijayabalaji, V., Goudar, K. S., Venkateshwarlu, K., and Amit, A. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis pa
  16. Tang, T., Targan, S. R., Li, Z. S., Xu, C., Byers, V. S., and Sandborn, W. J. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment.Pharmacol Ther 2011;33(2) PubMed
  17. Sandborn, W. J., Targan, S. R., Byers, V. S., Rutty, D. A., Mu, H., Zhang, X., and Tang, T. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol. 2013;108(1):90-98. PubMed
  18. Melchior, J., Palm, S., and Wikman, G. Controlled clinical study of standardized Andrographis paniculata extract in common cold - a pilot trial. Phytomedicine. 1997;3(4):315-318. PubMed
  19. Balap A, Atre B, Lohidasan S, et al. Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats. J Ethnopharmacol. 2016 May 13;183:9-17. PubMed
  20. Bertoglio JC, Baumgartner M, Palma R, et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study. BMC Neurol. 2016; 16(1):77. PubMed
  21. Suwankesawong W, Saokaew S, Permsuwan U, et al. Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database. BMC Complement Altern Med. 2014; 14:515. PubMed
  22. Ciampi E, Uribe-San-Martin R, Cárcamo C, et al. Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial. BMC Neurol 2020;20(1):173. PubMed
  23. Worakunphanich W, Thavorncharoensap M, Youngkong S, Thadanipon K, Thakkinstian A. Safety of Andrographis paniculata: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2021;30(6):727-739.
  24. More SJ, Tandulwadkar SS, Balap AR, Lohidasan S, Sinnathambi A, Mahadik KR. Effect of Andrographis paniculata extract and Andrographolide on the pharmacokinetics of Aceclofenac and Celecoxib in rats. Futur J Pharm Sci. 2023;9(1):1. PubMed
  25. Sundhani E, Nugroho AE, Nurrochmad A, Puspitasari I, Amalia Prihati D, Lukitaningsih E. Pharmacokinetic Herb-Drug Interactions of Glipizide with Andrographis paniculata (Burm. f.) and Andrographolide in Normal and Diabetic Rats by Validated HPLC Method. M PubMed
  26. Shang YX, Shen C, Stub T, et al. Adverse Effects of Andrographolide Derivative Medications Compared to the Safe use of Herbal Preparations of Andrographis paniculata: Results of a Systematic Review and Meta-Analysis of Clinical Studies. Front Pharmacol 20 PubMed

See these in context on the Andrographis monograph →

Thyme 18 references
  1. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-78. 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. Okazaki K, Kawazoe K, Takaishi Y. Human platelet aggregation inhibitors from thyme (Thymus vulgaris L.). Phytother Res 2002;16:398-9. .
  4. Spiewak R, Skorska C, Dutkiewicz J. Occupational airborne contact dermatitis caused by thyme dust. Contact Dermatitis 2001;44:235-9. . PubMed
  5. Ernst E, Marz R, Sieder C. A controlled multi-centre study of herbal versus synthetic secretolytic drugs for acute bronchitis. Phytomedicine 1997;4:287-93. PubMed
  6. Yamamoto J, Yamada K, Naemura A, et al. Testing various herbs for antithrombotic effect. Nutrition 2005;21(5):580-7. PubMed
  7. 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
  8. Mackiewicz, B., Skorska, C., Dutkiewicz, J., Michnar, M., Milanowski, J., Prazmo, Z., Krysinska-Traczyk, E., and Cisak, E. Allergic alveolitis due to herb dust exposure. Ann Agric Environ Med 1999;6(2):167-170.
  9. Martinez-Gonzalez, M. C., Goday Bujan, J. J., Martinez, Gomez W., and Fonseca, Capdevila E. Concomitant allergic contact dermatitis due to Rosmarinus officinalis (rosemary) and Thymus vulgaris (thyme). Contact Dermatitis 2007;56(1):49-50.
  10. Jukic, M., Politeo, O., Maksimovic, M., Milos, M., and Milos, M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother.Res 2007;21(3):259-261.
  11. Marzian, O. [Treatment of acute bronchitis in children and adolescents. Non-interventional postmarketing surveillance study confirms the benefit and safety of a syrup made of extracts from thyme and ivy leaves]. MMW.Fortschr.Med 6-28-2007;149(27-28 Suppl
  12. Cuzzolin, L. and Benoni, G. Attitudes and knowledge toward natural products safety in the pharmacy setting: an Italian study. Phytother.Res 2009;23(7):1018-1023. PubMed
  13. Berova, N., Stransky, L., and Krasteva, M. Studies on contact dermatitis in stomatological staff. Dermatol.Monatsschr. 1990;176(1):15-18.
  14. Smeenk, G., Kerckhoffs, H. P., and Schreurs, P. H. Contact allergy to a reaction product in Hirudoid cream: an example of compound allergy. Br.J Dermatol. 1987;116(2):223-231.
  15. Le Roy, R., Grosshans, E., and Foussereau, J. [Investigation of contact allergies in 100 cases of ulcus cruris (author's transl)]. Derm.Beruf.Umwelt. 1981;29(6):168-170.
  16. Lorenzi, S., Placucci, F., Vincenzi, C., Bardazzi, F., and Tosti, A. Allergic contact dermatitis due to thymol. Contact Dermatitis 1995;33(6):439-440. PubMed
  17. Bahadoran P, Rokni FK, Fahami F. Investigating the therapeutic effect of vaginal cream containing garlic and thyme compared to clotrimazole cream for the treatment of mycotic vaginitis. Iran J Nurs Midwifery Res 2010;15(Suppl 1):343-9.
  18. Erol S, Aydin B, Dilli D, Okumus N, Zenciroglu A, Gündüz M. An interesting newborn case of fructose 1-6 diphosphatase deficiency triggered after thyme juice ingestion. Clin Lab. 2014;60(1):151-3. PubMed

See these in context on the Thyme 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.
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  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
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  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
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See these in context on the Bitter Orange monograph →

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

© 2021 Therapeutic Research Center, LLC

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