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

Zhi Shi Ingredients & Drug Interactions

by Hawaii Pharm

Zhi Shi 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 Zhi Shi 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

Zhi Shi is a dietary supplement by Hawaii Pharm with 1 active ingredient. Its ingredients are commonly taken for weight loss, athletic performance and energy, digestive upset.Based on those ingredients, 957 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Citrus x aurantium Fruit Extract, Dry. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Zhi Shi by Hawaii Pharm

Ask about any prescription or over-the-counter medication and we check it for interactions with Zhi Shi by Hawaii Pharm — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Zhi Shi by Hawaii Pharm

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

From our pharmacy team — supplement deep dive

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

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 1 of its 1 active ingredient.
  • No proprietary blends here — you can verify the dose of every single component.

Zhi Shi contains one active ingredient: Citrus x aurantium Fruit Extract, Dry — also called bitter orange. This liquid form also includes alcohol, water, and glycerin as inactive ingredients to deliver the extract.

Does it work?

Couldn't assess
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 assessable

This is a single-ingredient Bitter Orange product and its label doesn't state a use — see Bitter Orange's own graded uses on its monograph.

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.

The evidence isn't established in our data for the uses Zhi Shi is promoted for — hay fever, hair loss, sexual dysfunction, pre-procedure anxiety, and athletic performance. All of these are rated as having insufficient reliable evidence to rate effectiveness.

That doesn't mean the product doesn't work; it means the clinical evidence isn't solid enough yet for us to say one way or the other.

The evidence, ingredient by ingredient 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 1 of the 1 matched ingredient.
  • Pregnancy & breastfeeding safety ratings cover 1 of 1.
  • General safety write-ups exist for 1 of 1.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Bitter orange taken by mouth in medicinal amounts carries real safety concerns. The most common side effects are high blood pressure and a fast heart rate, especially when combined with caffeine or other stimulants.

Rare but serious events reported in case reports include heart attack, seizure, stroke, fainting, abnormal heart rhythms, and dizziness. The product itself is rated possibly unsafe during pregnancy and breastfeeding, so those situations call for avoidance of supplement doses.

When applied to skin or inhaled as aromatherapy, bitter orange is generally well tolerated, though skin irritation can occur.

Side effects, ingredient by ingredient 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?
  • 1 of the 1 matched ingredient can interact with medications — Bitter Orange.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: diabetes medications; heart-rhythm medications.
  • For scale: 958 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 Zhi Shi, double-check the following with your pharmacist or our interaction tool: MAOIs (antidepressants), midazolam and other sedatives, heart rhythm medications, most medications processed by the liver (especially certain blood thinners, statins, and immunosuppressants), antidiabetes drugs, stimulants like pseudoephedrine, cough suppressants like dextromethorphan, and caffeine. The last item — caffeine — deserves special mention because bitter orange boosts each other's effects on your heart and blood pressure.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with no assessable stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This is a stimulant product — it's not for everyone, especially if you have heart disease, high blood pressure, or take medications that affect heart rhythm or blood pressure. Anyone taking prescription medications needs to check their specific drugs against our interaction tool before starting.

Talk with your pharmacist about whether it's right for you, and skip it entirely during pregnancy and breastfeeding.

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

Assessment coverage: 1 of 1 active ingredient matched to our full ingredient reviews (monographs). Based on the product label dated Oct 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 Zhi Shi, straight from the product label.

Brand Hawaii Pharm
Barcode (UPC) 840253659354
Net contents 4 Fluid Ounce(s); 120 mL
Market status On market
Date entered into DSLD Oct 24, 2023
DSLD ID 302022
Product type Botanical
Supplement form Liquid
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten 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 Zhi Shi by Hawaii Pharm, 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:
0.7 mL
Maximum serving Sizes:
1 mL
Servings per container
120
UPC/BARCODE
840253659354
IngredientAmount% DV
Citrus x aurantium Fruit Extract, Dry983 mg--

Other ingredients: Alcohol, Water, Glycerin

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.
Brand IP Statement(s)

Hawaii Pharm Herbal Extract Highest quality since 2008

Suggested/Recommended/Usage/Directions

Suggested use: Shake well before using. For adults add about 20-30 drops (0.7-1 mL, one full squeeze of the dropper bulb) to some juice or water, up to 4 times a day.

Precautions

Warning: We recommend to seek expert medical advice before taking.

Do not use if you are allergic to any ingredients.

Consult your physician before giving to children under 18, during pregnancy, if nursing or taking medications.

Consult your physician before giving to children under 18, during pregnancy, if nursing or taking medications.

May affect the ability to drive and operate machinery. May have contraindications, can cause side effects and adverse reactions. Do not use if seal is broken or missing.

Keep out of the reach of children!

Storage

Store in a cool dry place.

Seals/Symbols

cGMP Made in compliance with cGMP 21 CFR 111 in an FDA registered and inspected facility.

Organic Alcohol Based USA Made in United States of America

FDA Disclaimer Statement

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

General Statements

Scan this QR-code to get 15% discount on your next purchase. Limited time deal.

Formula

Citrus x aurantium

Organic Alcohol Based

Formulation

Only natural ingredients Purity is laboratory tested and verified

All the raw materials are gluten-free by their nature No artificial colors, flavors, or preservatives

Not tested on animals

Organic Alcohol Based

Made in USA, Hawaii

FDA Statement of Identity

Herbal Supplement

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

See for yourself

Zhi Shi by Hawaii Pharm label

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

Zhi Shi 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 Zhi Shi by Hawaii Pharm

This is the 1 active ingredient this product is made of. Select it to open its full monograph.

Serving size0.7 mL Dosage formLiquid Servings per container120 Amounts shown are per serving.

Citrus x aurantium Fruit Extract, Dry

Interacts with
957 drugs
983 mg per serving

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

Citrus x aurantium Fruit Extract, Dry monograph & interactions

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

Interaction report

Zhi Shi by Hawaii Pharm Drug Interactions

Want to check YOUR meds against Zhi Shi?

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
957Drugs
10 Major 876 Moderate 71 Minor

Ingredients driving the most interactions

Citrus x aurantium Fruit Extract, Dry 957

Individual Drug Interactions

The ingredients in Zhi Shi interact with 957 drugs. Click any drug to see the details.

1 of the 1 ingredient in Zhi Shi interact with drugs. Each result below shows which ingredient is responsible. Citrus x aurantium Fruit Extract, Dry

Each ingredient & the kinds of drugs it affects

For each ingredient in Zhi Shi with known interactions, here are the types of medications it can affect. Open any type for the detail — or search your exact drug in the checker above.

Citrus x aurantium Fruit Extract, Dry13 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
Citrus x aurantium Fruit Extract, Dry full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Zhi Shi, from the product label.

Hawaii Pharm

See all Hawaii Pharm products
Name
Hawaii Pharm LLC
Street Address
510 Sumner St. Ste. 613
City
Honolulu
State
HI
ZipCode
96817
Phone Number
888-854-2924
Web Address
www.hawaiipharm.com
Pharmacist Counseling Corner

Zhi Shi by Hawaii Pharm: Common Questions

Does Zhi Shi by Hawaii Pharm interact with any medications?
Yes. Based on its ingredients, Zhi Shi has a known interaction with 957 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?
Zhi Shi contains a single active ingredient, and that one ingredient can interact with many different medications on its own. We check it against each medication and show the mechanism 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 while pregnant or breastfeeding?
No — the safety data advises against supplement doses of bitter orange during both pregnancy and breastfeeding. Talk with your doctor or pharmacist for personalized advice if you're considering it in these situations.
What's bitter orange actually used for?
Zhi Shi is promoted for hay fever, hair loss, sexual dysfunction, anxiety before medical procedures, and athletic performance. However, we don't have strong clinical evidence that it works for any of these uses yet.
What are the most common side effects I might experience?
High blood pressure and a fast heart rate are the most common side effects when taken by mouth, particularly if you also drink caffeine or take stimulant medications. Dizziness, difficulty concentrating, and headache have also been reported.
Why does this interact with so many medications?
Bitter orange contains stimulant compounds (synephrine and octopamine) that affect your heart and blood pressure directly, and it also inhibits an enzyme in your liver (CYP3A4) that breaks down many medications — slowing their clearance and raising their blood levels.
Is this safe to take with caffeine?
No — combining bitter orange with caffeine increases both blood pressure and heart rate beyond what either one alone would do. Studies show this can happen even in otherwise healthy adults, so it's best avoided.

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

Not sure if Zhi Shi is safe with your meds?

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

Zhi Shi label
Go deeper

The Full Monographs Behind Zhi Shi’s Ingredients

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

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

Zhi Shi'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 47 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.

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.

© 2021 Therapeutic Research Center, LLC

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