Major interaction on record — check this product against your medications before combining. Based on 4 of 5 ingredients. Check your meds →
Dietary supplement

Immune Boost Ingredients & Drug Interactions

by JoySpring

Immune Boost label
See full label image
Liquid 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 Immune Boost 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

Immune Boost is a dietary supplement by JoySpring with 5 active ingredients. Its ingredients are commonly taken for psoriasis (topical), eczema and other skin conditions, digestive upset.Based on those ingredients, 1,423 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Oregon Grape, Bitter Orange, Echinacea purpurea. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Immune Boost by JoySpring

Ask about any prescription or over-the-counter medication and we check it for interactions with Immune Boost by JoySpring — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Immune Boost by JoySpring

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 Aug 6, 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 (1 mL) without saying how much of each component you get.

Immune Boost contains 5 active ingredients delivered in liquid form. The supplement includes a proprietary blend whose components are listed individually: Oregon grape (which contains berberine), echinacea purpurea (purple coneflower), elderberry, bitter orange, and red banded polypore.

The liquid also contains glycerin and purified water as inactive ingredients. Oregon grape and echinacea are traditionally used to support immune function, while elderberry is often taken for respiratory health.

Bitter orange provides stimulant compounds. Red banded polypore is a medicinal fungus used in traditional preparations.

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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Moderate

Some clinical evidence supports its ingredients for:

  • Psoriasis via Oregon Grape Possibly Effective
Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Psoriasis — rated "Possibly Effective" (Oregon Grape) (Natural Medicines).

The evidence for these ingredients' effectiveness is limited. For Oregon grape, there is possibly effective evidence for psoriasis when used topically, but for oral use — which is what this supplement is — the data on eczema, indigestion, and peptic ulcers rates as insufficient.

Echinacea's evidence for anxiety, athletic performance, ADHD, burns, chronic fatigue, and migraines is insufficient to establish whether it works. Elderberry similarly shows insufficient evidence for hay fever, heart disease, chronic fatigue, COPD, cognitive function, and lower respiratory infections.

Bitter orange has insufficient evidence for hay fever, hair loss, sexual function, anxiety, and athletic performance. We hold no effectiveness data for red banded polypore.

The evidence, ingredient by ingredient Oregon Grape Echinacea Elderberry 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 4 of the 4 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 4 of 4.
  • General safety write-ups exist for 4 of 4.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Oregon grape is generally well tolerated when applied to skin, but oral use is less well studied and requires caution. Echinacea is generally well tolerated short-term but may trigger allergic reactions, especially in people sensitive to ragweed and related plants; rare cases of echinacea-induced hepatitis have been reported.

Common side effects with echinacea include abdominal pain, constipation, diarrhea, heartburn, nausea, rashes, and stomach upset. Elderberry made from properly cooked fruit is generally well tolerated, but raw or unripe berries and other plant parts contain toxins that can cause nausea, vomiting, severe diarrhea, weakness, dizziness, numbness, and stupor.

Bitter orange may be unsafe when used in medicinal amounts and commonly raises blood pressure and heart rate, especially with caffeine; rare serious effects include heart attack, QT prolongation, seizure, stroke, and irregular heartbeats. Pregnancy and breastfeeding: Oregon grape is likely unsafe in pregnancy and while breastfeeding — berberine may pass to infants.

Echinacea is possibly safe in pregnancy but breastfeeding data is missing. Elderberry is listed as likely safe in both pregnancy and breastfeeding.

Bitter orange is listed as likely safe in pregnancy but possibly unsafe during breastfeeding. Red banded polypore has no pregnancy or breastfeeding data on file.

Side effects, ingredient by ingredient Oregon Grape Echinacea Elderberry 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?
  • 4 of the 4 matched ingredients can interact with medications — Elderberry, Oregon Grape, Bitter Orange, Echinacea.
  • 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: 1,424 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, double-check these medication types with your doctor or pharmacist: monoamine oxidase inhibitors (MAOIs) — major risk of dangerously high blood pressure; sedatives like midazolam (Versed), CNS depressants, and sleep aids; blood pressure medications; blood thinners and antiplatelet drugs; medications for diabetes; liver-metabolized drugs (especially those processed by CYP3A4, CYP2D6, or CYP2C9); immunosuppressants like cyclosporine; cancer drugs including etoposide and pazopanib; and stimulant drugs or high-caffeine products. No interactions are documented for the red banded polypore ingredient we could check.

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 behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.

This product is best approached cautiously because several of its ingredients carry Moderate interactions with common medications and one carries a Major interaction. If you take any prescription or over-the-counter drugs — especially blood pressure medications, blood thinners, diabetes drugs, antidepressants (including MAOIs), stimulants, or immunosuppressants — talk with your doctor or pharmacist before starting it.

Pregnant or breastfeeding individuals should also check with their healthcare provider first, since some ingredients carry safety concerns at those times.

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

Assessment coverage: 4 of 5 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated May 24, 2023.

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 Immune Boost, straight from the product label.

Brand JoySpring
Barcode (UPC) 850008889219
Net contents 30 Milliliter(s); 1 Fluid Ounce(s)
Market status On market
Date entered into DSLD May 24, 2023
DSLD ID 295911
Product type Botanical
Supplement form Liquid
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Children 4 or More Years of Age, Adult (18 - 50 Years), Gluten Free, Sugar Free, Children more than 1 but less than 4
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 Immune Boost by JoySpring, 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 mL
Maximum serving Sizes:
3 mL
Servings per container
30
UPC/BARCODE
850008889219
IngredientAmount% DV
Proprietary Blend1 mL--
Oregon Grape0 NP--
Echinacea purpurea0 NP--
Elderberry0 NP--
Bitter Orange0 NP--
Red Banded Polypore0 NP--

Other ingredients: Glycerin, Water, Purified

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 daily or as needed. Shake well. Use only under adult supervision.

2-8 years - 1 dropper 9-15 years - 1-2 droppers 16+ years - 2-3 droppers 1 dropper = 1 squeeze

Precautions

Use only under adult supervision.

Warning: Consult your physician before use.

Keep out of reach of children.

Do not use if the product appears to be tampered with or if seal is broken.

Not intended for children under 2 years of age.

Storage

Store at room temperature, away from light.

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.

Formulation

Gluten free Sugar free

May support immunity

Formula

Echinacea herbal formula

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Immune Boost by JoySpring label

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

Immune Boost 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 Immune Boost by JoySpring

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

Serving size1 mL Dosage formLiquid Servings per container30 Amounts shown are per serving.

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

Proprietary Blend

1 mL per serving

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

Interaction report

Immune Boost by JoySpring Drug Interactions

Want to check YOUR meds against Immune Boost?

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
1,423Drugs
10 Major 1,412 Moderate 1 Minor

Ingredients driving the most interactions

Oregon Grape 1,218
Bitter Orange 957
Echinacea purpurea 816
Elderberry 121

Individual Drug Interactions

The ingredients in Immune Boost interact with 1,423 drugs. Click any drug to see the details.

4 of the 5 ingredients in Immune Boost interact with drugs. Each result below shows which ingredient is responsible. Oregon Grape Bitter Orange Echinacea purpurea Elderberry

Each ingredient & the kinds of drugs it affects

For each ingredient in Immune Boost 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.

Oregon Grape9 drug types · 1,218 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Oregon grape might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, Oregon grape might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Clinical research suggests that berberine, a constituent of Oregon grape, can lower blood glucose levels.

Likelihood Possible Evidence A
Antihypertensive Drugs

Theoretically, Oregon grape might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research suggests that berberine, a constituent of Oregon grape, can have hypotensive effects. Also, an analysis of clinical evidence suggests that taking berberine in combination with amlodipine (Norvasc) can lower systolic and diastolic blood pressure when compared with taking amlodipine alone.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, Oregon grape might increase the sedative effects of CNS depressants.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, Oregon grape might increase the effects and adverse effects of cyclosporine.
Berberine, a constituent of Oregon grape, can reduce metabolism of cyclosporine and increase serum levels. It might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine.

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9).

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6).

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, Oregon grape might increase serum levels of drugs that are P-glycoprotein (P-gp) substrates.
In vitro research suggests that Oregon grape extracts inhibit P-gp efflux.

Likelihood Possible Evidence D
Oregon Grape 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

Echinacea purpurea12 drug types · 816 drugs

Caffeine

Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
Echinacea seems to increase plasma concentrations of caffeine by around 30%. This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.

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

Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30%. Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.

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

Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir. However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4. The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4. In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate.

Likelihood Possible Evidence B
Etoposide (Vepesid)

Echinacea may increase levels of etoposide.
In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism. Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme.

Likelihood Possible Evidence D
Immunosuppressants

Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.
Theoretically, echinacea may interfere with immunosuppressant therapy because of its immunostimulant activity.

Likelihood Possible Evidence B
Darunavir (Prezista)

Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.
Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients.

Likelihood Unlikely Evidence B
Dayquil Severe

Echinacea is reported to have varying effects on a number of Cytochrome P450 metabolizing enzymes in the liver, including CYP1A2 and CYP3A4, which play a role in acetaminophen and dextromethorphan metabolism (both contained in DayQuil Severe), respectively. Studies have reported both enzyme inhibition and induction, making it difficult to predict clinically significant drug interactions with reliability. Specific drug interaction studies reporting definitive results are rare, and potential drug interactions involving echinacea should likely be taken on a case-by-case basis. Based on what we know about how acetaminophen and dextromethorphan are metabolized, the risk of a clinically significant interaction between echinacea and DayQuil Severe is low.

Likelihood Unlikely Evidence A
Docetaxel (Taxotere)

Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.
Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study.

Likelihood Unlikely Evidence B
Etravirine (Intelence)

Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.
Etravirine is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg three times daily for 14 days did not alter the pharmacokinetics of etravirine in HIV-infected patients.

Likelihood Unlikely Evidence B
Lopinavir/Ritonavir (Kaletra)

Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.
Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers.

Likelihood Unlikely Evidence B
Midazolam (Versed)

Theoretically, echinacea may increase the metabolism of intravenous midazolam.
Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam. Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.
Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR.

Likelihood Possible Evidence B
Echinacea purpurea full monograph & interactions

Elderberry2 drug types · 121 drugs

Immunosuppressants

Theoretically, elderberry might interfere with immunosuppressant therapy due to its immunostimulant activity.
Elderberry has immunostimulant activity, increasing the production of cytokines, including interleukin and tumor necrosis factor.

Likelihood Possible Evidence B
Pazopanib (Votrient)

Theoretically, elderberry might interact with pazopanib, potentially increasing the risk of adverse effects.
In one case, a 65-year-old patient taking pazopanib for 4 weeks for soft-tissue sarcoma developed severe nausea, loose stools, and elevated alanine transaminase and aspartate transaminase levels and was diagnosed with grade 3 liver injury. The patient reported taking elderberry supplements for 2 years, dose unspecified, and was also taking a multivitamin and a calcium supplement. The patient's symptoms and liver enzyme levels improved upon discontinuation of pazopanib and all supplements. Pazopanib treatment was re-initiated, at a lower dose, with no further evidence of liver injury. It was unclear in this case report if the elderberry supplements were derived from the berry, the flower, or the combination.

Likelihood Possible Evidence D
Elderberry full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Immune Boost, from the product label.

JoySpring

See all JoySpring products
Name
JoySpring
Street Address
PO Box 656
City
Waxhaw
State
NC
ZipCode
28173
Web Address
joyspringvitamins.com
Pharmacist Counseling Corner

Immune Boost by JoySpring: Common Questions

Does Immune Boost by JoySpring interact with any medications?
Yes. Based on its ingredients, Immune Boost has a known interaction with 1,423 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?
Immune Boost 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 this if I'm pregnant or breastfeeding?
Oregon grape is not safe — it's likely unsafe in pregnancy and while breastfeeding. Echinacea is possibly safe during pregnancy but we don't have breastfeeding data. Elderberry is listed as likely safe for both. Bitter orange may be safe in pregnancy but is possibly unsafe while breastfeeding. Talk with your doctor or pharmacist about whether this product is right for you at this time.
What are the most common side effects?
Echinacea most commonly causes abdominal pain, constipation, diarrhea, heartburn, nausea, rashes, and stomach upset. Bitter orange commonly raises blood pressure and heart rate. Elderberry from properly cooked berries is well tolerated, though nausea and vomiting have been reported in one case involving a combined elderberry-echinacea product. Allergic reactions to echinacea, though uncommon, can be serious for people sensitive to ragweed.
Is this safe for people with a weakened immune system?
No — both echinacea and elderberry have immunostimulant activity that could interfere with immunosuppressant medications or therapies. If you're on immune-suppressing drugs (like those after an organ transplant) or have a condition requiring such treatment, check with your doctor before using this product.
Will this work to boost my immune system?
We don't have strong evidence that any of these ingredients reliably boost immunity. Most have insufficient evidence for their common uses — echinacea and elderberry are often promoted for colds and flu, but the data we hold doesn't establish that they work for those purposes. If you're considering this for a specific reason, talk it over with your healthcare provider.
Can I take this with my blood pressure medication?
Not safely without checking first. Oregon grape and bitter orange both have compounds that can lower blood pressure, and taking them together with blood pressure meds could cause dangerously low readings. Talk with your doctor or pharmacist before combining them.
What if I'm allergic to ragweed?
Echinacea can trigger allergic reactions in people sensitive to ragweed and related plants (chrysanthemums, marigolds, daisies). If you have that sensitivity, avoiding this product is wise. If you're not sure, ask your doctor or pharmacist.

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

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The Full Monographs Behind Immune Boost’s Ingredients

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

Herb & supplement monograph

Oregon Grape

Interacts with 1,218 drugs

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for...

Read the full Oregon Grape monograph → Herb & supplement monograph

Echinacea

Interacts with 816 drugs

Echinacea is a popular herb taken to help prevent or shorten the common cold, but study results are mixed and the overall benefit appears small at best. It is generally well tolerated for sh...

Read the full Echinacea monograph → Herb & supplement monograph

Elderberry

Interacts with 121 drugs

Elderberry is a popular herbal supplement, mainly taken to help with colds and flu. Some small studies suggest it may modestly shorten cold or flu symptoms, but the evidence is limited and n...

Read the full Elderberry 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

Immune Boost'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 125 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.

Oregon Grape 21 references
  1. Wiesenauer M, Lydtke R. Mahonia aquifolium in patients with Psoriasis vulgaris; an intraindividual study. Phytomedicine 1996;3:231-5.
  2. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate 1993;63:201-8. PubMed
  3. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  4. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  5. Gulliver WP, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10% topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther 2005;12:398-406. PubMed
  6. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008;93:2559-65. PubMed
  7. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  8. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  9. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  10. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  11. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  12. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
  13. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  14. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  15. Zhang, H., Wei, J., Xue, R., Wu, J. D., Zhao, W., Wang, Z. Z., Wang, S. K., Zhou, Z. X., Song, D. Q., Wang, Y. M., Pan, H. N., Kong, W. J., and Jiang, J. D. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin re
  16. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  17. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., and Guan, Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndro
  18. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
  19. Chun YT, Yip TT, Lau KL, and et al. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmac 1979;10:177-182. PubMed
  20. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. PubMed
  21. Fan Y, Zhou Z, Zhang L. Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines. J Pharm Pharm Sci 2024;26:11927. PubMed

See these in context on the Oregon Grape monograph →

Echinacea 51 references
  1. Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998;168:170-1. PubMed
  2. Mullins RJ. Allergic reactions to Echinacea. J Allergy Clin Immunol 2000;104:S340-341 (Abstract 1003).
  3. Chavez ML, Chavez PI. Echinacea. Hosp Pharm 1998;33:180-8.
  4. Grimm W, Muller HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections. Am J Med 1999;106:138-43. PubMed
  5. Taylor JA, Weber W, Standish L, et al. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. JAMA 2003;290:2824-30.. PubMed
  6. Luettig B, Steinmuller C, Gifford GE, et al. Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 1989;81:669-75. PubMed
  7. Stimpel M, Proksch A, Wagner H, et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845-9. PubMed
  8. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  9. Gallo M, Sarkar M, Au W, et al. Pregnancy outcome following gestational exposure to echinacea: A prospective controlled study. Arch Intern Med 2000;160:3141-3. PubMed
  10. Soon SL, Crawford RI. Recurrent erythema nodosum associated with echinacea herbal therapy. J Am Acad Dermatol 2001;44:298-9. PubMed
  11. Mullins RJ, Heddle R. Adverse reactions associated with echinacea: the Australian experience. Ann Allergy Asthma Immunol 2002;88:42-51. PubMed
  12. Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9.
  13. Schulten B, Bulitta M, Ballering-Bruhl B, et al. Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial. Arzneimittelforschung 2001;51:563-8.. PubMed
  14. Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
  15. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med 2004;164:1237-41. PubMed
  16. Gorski JC, Huang S, Zaheer NA, et al. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo.Clin Pharmacol Ther 2003;73 (Abstract PDII-A-8):P94. PubMed
  17. Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol 2004;140:723-7. PubMed
  18. Goel V, Lovlin R, Barton R, et al. Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther 2004;29:75-83.
  19. Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine 2003;10:66-86. PubMed
  20. Huntley AL, Thompson Coon J, Ernst E. The safety of herbal medicinal products derived from Echinacea species: a systematic review. Drug Saf 2005;28:387-400. PubMed
  21. Turner RB, Bauer R, Woelkart K, et al. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005;353:341-8.
  22. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  23. Perri D, Dugoua JJ, Mills E, Koren G. Safety and efficacy of echinacea (Echinacea augustafolia, e. purpurea and e. pallida) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e262-7.
  24. Kocaman O, Hulagu S, Senturk O. Echinacea-induced severe acute hepatitis with features of cholestatic autoimmune hepatitis. Eur J Intern Med 2008;19:148. PubMed
  25. Barrett B, Brown R, Rakel D. et al. Echinacea for treating the common cold: a randomized trial. Ann Intern Med 2010;153:769-77. PubMed
  26. Press Release: Echinacea herbal products should not be used in children under 12 years old. Medicines and Healthcare Products Regulatory Agency (UK). August 20, 2012. Available at: www.mhra.gov.uk/NewsCentre/Pressreleases/CON180627. (Accessed 21 October
  27. Barrett B, Brown R, Rakel D, Rabago D, et al. Placebo effects and the common cold: a randomized controlled trial. Ann.Fam.Med 2011;9:312-22. PubMed
  28. Haller J, Freund, TF, Pelczer, KG, et al. The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers. Phytother.Res. 2013;27:54-61.
  29. Grbic J, Wexler I, Celenti R, et al. A phase II trial of a transmucosal herbal patch for the treatment of gingivitis. J Am Dent.Assoc. 2011;142:1168-75. PubMed
  30. Schapowal A, Berger D, Klein P, et al. Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a randomized double-blind trial. Eur.J Med Res 9-1-2009;14:406-12. PubMed
  31. Bossaer JB and Odle BL. Probable etoposide interaction with Echinacea. J.Diet.Suppl 2012;9:90-5.
  32. Abdul MI, Jiang X, Williams KM, et al. Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. Br J Clin.Pharmacol. 2010;69:508-15. PubMed
  33. Kemp, D. E. and Franco, K. N. Possible leukopenia associated with long-term use of echinacea. J Am Board Fam.Pract. 2002;15(5):417-419.
  34. Liatsos, G., Elefsiniotis, I., Todorova, R., and Moulakakis, A. Severe thrombotic thrombocytopenic purpura (TTP) induced or exacerbated by the immunostimulatory herb Echinacea. Am J Hematol. 2006;81(3):224.
  35. Penzak, S. R., Robertson, S. M., Hunt, J. D., Chairez, C., Malati, C. Y., Alfaro, R. M., Stevenson, J. M., and Kovacs, J. A. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy s
  36. Maskatia, Z. K. and Baker, K. Hypereosinophilia associated with echinacea use. South.Med J 2010;103(11):1173-1174. PubMed
  37. Parnham MJ. Benefit-risk assessment of the squeezed sap of the purple coneflower (Echinacea purpurea) for long-term oral immunostimulation. Phytomed 1996;3:95-102. PubMed
  38. Schroder-Aasen T, Molden G, Nilsen OG. In vitro inhibition of CYP3A4 by the multiherbal commercial product Sambucus Force and its main constituents Echinacea purpurea and Sambucus nigra. Phytother Res 2012;26(11):1606-13.
  39. Moltó J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 2011;55(1):326-30.
  40. Goey AK, Meijerman I, Rosing H, et al. The effect of Echinacea purpurea on the pharmacokinetics of docetaxel. Br J Clin Pharmacol 2013;76(3):467-74.
  41. Moltó J, Valle M, Miranda C, et al. Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients. Antimicrob Agents Chemother 2012;56(10):5328-31. PubMed
  42. Lawrenson JA, Walls T, Day AS. Echinacea-induced acute liver failure in a child. J Paediatr Child Health 2014;50(10):841.
  43. Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008;103:445-9.
  44. Gabranis I, Koufakis T1, Papakrivos I, Batala S. Echinacea-associated acute cholestatic hepatitis. J Postgrad Med. 2015;61(3):211-2. PubMed
  45. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  46. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev.2014;(2):CD000530. doi: 10.1002/14651858.CD000530.pub3. PubMed
  47. Hoban CL, Byard RW, Musgrave IF. Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015. J Integr Med. 2019;17(5):338-343. PubMed
  48. Ogal M, Johnston SL, Klein P, Schoop R. Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial. Eur J Med Res. 2021 Apr 8;26(1):33. PubMed
  49. Lopresti AL, Smith SJ. An investigation into the anxiety-relieving and mood-enhancing effects of Echinacea angustifolia (EP107 ™): A randomised, double-blind, placebo-controlled study. J Affect Disord 2021;293:229-237.
  50. Weishaupt R, Buchkov A, Kolev E, Klein P, Schoop R. Reduction of viral load in patients with acute sore throats: Results from an observational clinical trial with Echinacea / Salvia lozenges [published online ahead of print, 2023 Mar 8]. Complement Med Re
  51. Sumer J, Keckeis K, Scanferla G, et al. Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial. Front Med (Lausanne) 2023;10:948787. PubMed

See these in context on the Echinacea monograph →

Elderberry 6 references
  1. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw 2001;12:290-6..
  2. Elderberry (Sambucus species). The Poison Plant Patch, Novia Scotia Museum, 2007. Available at: http://museum.gov.ns.ca/poison/?section=species&id=117 (Accessed 16 October 2009).
  3. European elder. Canadian Poisonous Plants Information System. Available at: http://www.cbif.gc.ca/pls/pp/ppack.jump?p_null=all&p_psn=121&p_type=all&p_sci=comm&p_x=px (Accessed 16 October 2009).
  4. Raus K, Pleschka S, Klein P, Schoop R, Fisher P. Effect of an echinacea-based hot drink versus oseltamivir in Influenza treatment: a randomized, double-blind, double-dummy, multicenter, noninferiority clinical trial. . Curr Ther Res Clin Exp. 2015;20;77:6 PubMed
  5. Ramachandran A, Antala D, Pudasainee P, Panginikkod S, Gupta H. A Plausible Association Between the Use of Elderberry and Autoimmune Hepatitis. Cureus 2022;14(4):e24250. PubMed
  6. Agarwal N, Mangla A. Elderberry interaction with pazopanib in a patient with soft-tissue sarcoma: A case report and literature review. Mol Clin Oncol 2024;20(5):36. PubMed

See these in context on the Elderberry 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 →

Parts of this content are provided by the Therapeutic Research Center, LLC.

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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