Home Ingredients Methylsynephrine (Oxilofrine)

Methylsynephrine (Oxilofrine)

Evidence Level
Preliminary
8 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

Methylsynephrine is a label name for oxilofrine (also called p-hydroxyephedrine), a synthetic stimulant drug that has been sold in pre-workout and fat-burner products. In some countries oxilofrine is a prescription medicine given to stimulate the heart and raise blood pressure, at doses of 16 to 40 mg, but it has never been approved in the US. The US FDA states that methylsynephrine does not meet the legal definition of a dietary ingredient, so supplements that declare it are misbranded, and it has sent warning letters to companies selling them. The World Anti-Doping Agency prohibits it in competition, and the US Department of Defense bars it. Product testing found it missing from about half of the products labeled with it and at drug-level or higher doses in others. No human trial of it as a supplement has been published; the human data come from older drug studies.

Studied Dose Single oral doses of 16, 32 and 64 mg (absorption study) and 120 mg (heart study) in drug research; prescribed doses abroad are cited at 16 to 40 mg. Tested supplements held up to 75 mg per serving. No safe dose is established.
Active Compound Oxilofrine (methylsynephrine, p-hydroxyephedrine; 4-[1-hydroxy-2-(methylamino)propyl]phenol), a synthetic sympathomimetic stimulant drug. Not the same compound as p-synephrine from bitter orange.

Benefits

Blood pressure on standing in older prescription drug trials

As a prescription drug, oxilofrine was tested in people whose blood pressure regulation falters on standing. In a 2 week double-blind trial in 60 patients, a standing blood pressure measure rose 48% with the drug versus 21% with placebo. A systematic review listed it among treatments that improved the drop on standing but judged most trials in this field poor quality. This is drug research, not supplement use.

Supported by Trial 1, Trial 4

Heart contraction and blood pressure after a single 120 mg dose

In 8 healthy volunteers given one 120 mg oral dose of oxilofrine, heart rate and mean blood pressure did not change, systolic pressure rose by up to 13.8% and diastolic fell by up to 8.8%, and ultrasound measures of heart contraction rose by about 21 to 30%, tracking blood levels of the drug. A single small drug study; the abstract reports no placebo group.

Supported by Trial 2, Trial 1

Absorption and blood levels after single oral doses

In 12 healthy men given single oral doses of 16, 32 and 64 mg, blood levels rose faster than the dose (median peaks of about 11, 31 and 123 ng/mL), pointing to first-pass breakdown that becomes saturated at higher doses. Peaks came within about 1 to 2 hours, about half of each dose appeared in urine, and no side effects were reported. A drug study led from a drug company's clinical research department.

Supported by Trial 3

Exercise performance, energy and body weight

These are the uses methylsynephrine products were sold for, yet no published human trial of methylsynephrine or oxilofrine for exercise performance, energy or body weight was found in PubMed, and ClinicalTrials.gov lists no registered trial. In a cell study it blocked the noradrenaline transporter in a way the researchers likened to amphetamine. The human data come only from older drug studies.

Supported by Trial 5, Trial 6

Mechanism of action

1

Releases noradrenaline from nerve stores (rat studies)

In isolated rat heart and spleen tissue, oxilofrine strongly inhibited the storage of noradrenaline and released it from storage, mainly newly made noradrenaline, while speeding up its production, which raised transmitter levels around the receptors. These are animal and tissue findings.

2

Amphetamine-like action at the noradrenaline transporter (cell study)

In human cells engineered to carry monoamine transporters, methylsynephrine blocked the noradrenaline transporter and, less strongly, the dopamine transporter, a pattern the researchers likened to amphetamine. None of the pre-workout compounds tested blocked the serotonin transporter. Cell work only.

3

Stimulates heart contraction in human drug studies

After a single 120 mg oral dose in healthy volunteers, oxilofrine increased the strength of heart contraction on ultrasound for a long period without raising heart rate, and the effect closely followed blood levels of the drug. The US Department of Defense's supplement safety program describes it as a stimulant that increases blood pressure and affects heart rate.

Clinical trials

1
Oxilofrine vs Placebo for 2 Weeks in Orthostatic Circulatory Disorders: Double-Blind Drug Trial
PubMed

Double-blind, placebo-controlled trial of the prescription drug oxilofrine after a 1 week washout; the listed affiliation includes the drug company Albert-Roussel-Pharma GmbH. Article in German with an English abstract. (Pohl et al. 1991, Fortschr Med)

60 patients with orthostatic circulatory regulation disorders of the sympathicotonic type (30 oxilofrine, 30 placebo).

The primary measure, the area of blood pressure amplitude in the Schellong standing test, rose 48% with oxilofrine (126 to 187 mmHg x min) versus 20.8% with placebo, a significant difference. Systolic pressure on standing stayed nearly constant with oxilofrine and fell with placebo. The abstract does not state the dose. Drug research in patients, not supplement use.

2
Single 120 mg Oral Dose in Healthy Volunteers: Blood Levels and Heart Function
PubMed

Combined pharmacokinetic and clinical study relating blood levels of oxilofrine to blood pressure, heart rate and echocardiographic measures. (Kauert et al. 1988, Int J Clin Pharmacol Res)

8 healthy volunteers.

Blood levels showed a second peak between hours 2 and 3, consistent with enterohepatic recycling. Heart rate and mean arterial pressure did not change and peripheral resistance fell on average; systolic pressure rose by up to 13.8% and diastolic fell by up to 8.8%. Fractional shortening of the left ventricle rose 20.9% and its velocity 29.5%, correlating closely with blood levels (r = 0.981).

3
Single 16, 32 and 64 mg Doses: Dose Linearity and Bioavailability
PubMed

Open Latin-square study with 1 week between dosing days, from the clinical research department of Hoechst AG. (Verho et al. 1988, Int J Clin Pharmacol Res)

12 healthy male volunteers given 16, 32 and 64 mg tablets and 16 mg drops.

Median peak blood levels were 11.4, 31.4 and 122.9 ng/mL for the 16, 32 and 64 mg tablets, reached within 0.7 to 1.7 hours, and exposure rose faster than the dose, suggesting saturable first-pass metabolism. About 50% of each dose was recovered in urine. No side effects were reported.

4
Systematic Review of Treatments for Orthostatic Hypotension: 36 Placebo-Controlled Trials
PubMed

Systematic review of randomized, placebo-controlled trials of drug and non-drug treatments that measured the blood pressure drop on standing. (Logan et al. 2012, Age Ageing)

36 trials covering 21 interventions in heterogeneous patient groups; no meta-analysis was possible.

Most trials were of poor quality with a high risk of bias, and changes in the standing drop and in symptoms were often inconsistent. Oxilofrine was among the treatments that improved the drop on standing. The authors concluded that many recommended treatments have a limited evidence base. Drug evidence in patients only.

5
Product Analysis, Not a Trial: Oxilofrine in 27 US Supplements Labeled Methylsynephrine
PubMed

Validated UHPLC mass spectrometry analysis of supplements sold in the US whose labels listed methylsynephrine. (Cohen et al. 2017, Drug Test Anal)

27 brands of dietary supplements; no human participants.

Oxilofrine was present in 14 brands (52%) at 0.0003 to 75 mg per serving, and 6 of those 14 contained pharmaceutical or greater doses. Following label directions, a consumer could take as much as 250 mg a day. The paper notes that oxilofrine is prescribed at 16 to 40 mg, has never been approved in the US, and that athletes have tested positive for it.

6
Product Analysis, Not a Trial: FDA Testing of 59 Bitter Orange Products
PubMed

LC-MS/MS analysis by FDA scientists of products labeled to contain bitter orange or its amines. (Pawar et al. 2020, Drug Test Anal)

59 dietary supplements sold in the US; no human participants.

The synthetic amine methylsynephrine, whose effects in humans the authors call unknown, was found in 6 products at up to 240 mg per daily serving. The authors state that methylsynephrine is not permitted in dietary supplements. Only 5 of 23 products with a synephrine claim were within 80 to 120% of the label.

7
Case Reports and Product Analysis, Not a Trial: The Dexaprine Supplement
PubMed

Analysis by the Dutch public health institute of tablets from a supplement removed from the Dutch market after reports to the Dutch Poisons Information Center. (Venhuis et al. 2014, Drug Test Anal)

Leftover tablets from 4 patients, sent in by health care professionals.

Reports described nausea, agitation, fast heart rate and palpitations after as little as half a tablet, and one cardiac arrest. The tablets contained synephrine, oxilofrine, deterenol, yohimbine, caffeine and theophylline, plus two compounds tentatively identified as beta-methyl-beta-phenylethylamines. A multi-stimulant product cannot single out oxilofrine as the cause.

8
Product Analysis, Not a Trial: Stimulant Cocktails in 17 Supplements Labeled Deterenol
PubMed

Analysis of US supplements labeled as containing deterenol, with each brand tested by two laboratories in the US and the Netherlands and discrepancies rechecked in Belgium; a correction to the paper was later published. (Cohen et al. 2021, Clin Toxicol (Phila))

17 brands of sports and weight-loss supplements; no human participants.

Nine prohibited stimulants were found, with up to 4 in one product; oxilofrine was present at 18 to 55 mg per recommended serving. The authors note that such stimulant cocktails have never been tested in humans and that their safety is unknown.

Side effects and drug interactions

Common Potential side effects

The US Department of Defense's supplement safety program describes methylsynephrine as a stimulant that increases blood pressure and affects heart rate, and says the effects of large amounts, or of combining it with other stimulants, are not fully known. As oxilofrine it is a drug given to raise blood pressure.
Labels are unreliable: of 27 US brands labeled with methylsynephrine, 14 contained it, at 0.0003 to 75 mg per serving; 6 held pharmaceutical or greater doses, and label directions allowed up to 250 mg a day. FDA scientists found up to 240 mg per daily serving in bitter orange products.
A Dutch supplement, Dexaprine, containing oxilofrine with synephrine, deterenol, yohimbine and caffeine, was linked to nausea, agitation, fast heart rate, palpitations and one cardiac arrest, sometimes after half a tablet. The multi-stimulant mix cannot single out oxilofrine.
Prohibited in competition by the World Anti-Doping Agency, listed as oxilofrine (methylsynephrine) under specified stimulants (2026 list), and on the US Department of Defense prohibited dietary supplement ingredient list. Undeclared oxilofrine has been found at high levels in sports supplements sold online in the Netherlands.
The US FDA states that methylsynephrine is not a dietary ingredient, so supplements declaring it are misbranded.
There is no safety testing of it as a supplement, so there is no basis for use during pregnancy or breastfeeding, by children and adolescents, or by people with heart or blood-pressure conditions.

Important Drug interactions

Caffeine and other stimulants (synephrine, deterenol, yohimbine and similar pre-workout ingredients): products have combined up to 4 prohibited stimulants, mixes never tested in humans, and the effects of combining methylsynephrine with other stimulants are not fully known.
Blood-pressure medicines: oxilofrine is a drug used to raise blood pressure and is described as increasing blood pressure and affecting heart rate, so it may work against these medicines.

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Frequently asked questions about Methylsynephrine (Oxilofrine)

Is methylsynephrine legal in US dietary supplements?

No, according to the FDA. The agency states that methylsynephrine (oxilofrine) does not meet the legal definition of a dietary ingredient, so supplements that declare it are misbranded. In March 2016 it sent warning letters to 7 companies over 8 products and repeated the point to one of them in 2017. Oxilofrine has never been approved as a drug in the US either.

Is methylsynephrine the same as synephrine from bitter orange?

No. Despite the similar name, methylsynephrine is oxilofrine, a synthetic stimulant drug, while p-synephrine is a natural amine in bitter orange. FDA scientists testing bitter orange products classed methylsynephrine as a synthetic amine and found it in 6 products at up to 240 mg per daily serving. Sport rules differ too: the World Anti-Doping Agency prohibits oxilofrine in competition but only monitors synephrine.

Can athletes or service members use methylsynephrine?

Athletes subject to anti-doping rules should not. Oxilofrine (methylsynephrine) is on the World Anti-Doping Agency's 2026 Prohibited List as a specified stimulant banned in competition, and methylsynephrine is on the US Department of Defense prohibited dietary supplement ingredient list. Undeclared oxilofrine has also turned up in sports supplements, so a product need not list it to carry the risk of a positive test.

Do products labeled methylsynephrine contain what the label says?

Often not. In a test of 27 US brands labeled with methylsynephrine, only 14 contained it, at anywhere from 0.0003 to 75 mg per serving, and 6 of those held pharmaceutical or greater doses; following the label, a person could take up to 250 mg a day. Prescription doses of oxilofrine are 16 to 40 mg.

What is Methylsynephrine?

Methylsynephrine is a label name for oxilofrine (also called p-hydroxyephedrine), a synthetic stimulant drug that has been sold in pre-workout and fat-burner products.

What is Methylsynephrine used for?

NutraSmarts does not list Methylsynephrine under a health category. What the research covers: As a prescription drug, oxilofrine was tested in people whose blood pressure regulation falters on standing. In a 2 week double-blind trial in 60 patients, a standing blood pressure measure rose 48% with the drug versus 21% with placebo.

What doses of Methylsynephrine have been studied?

Methylsynephrine is a drug or research chemical, not a dietary supplement: it is a prescription medicine in some countries, is not approved for sale as a supplement in the US, or has a regulatory warning against it. Doses used in studies: Single oral doses of 16, 32 and 64 mg (absorption study) and 120 mg (heart study) in drug research; prescribed doses abroad are cited at 16 to 40 mg. Tested supplements held up to 75 mg per serving. No safe dose is established. This is not dosing advice.

Is Methylsynephrine safe, and does it have side effects?

Methylsynephrine is a drug or research chemical, not a dietary supplement: it is a prescription medicine in some countries, is not approved for sale as a supplement in the US, or has a regulatory warning against it. Side effects and cautions reported for Methylsynephrine include: The US Department of Defense's supplement safety program describes methylsynephrine as a stimulant that increases blood pressure and affects heart rate, and says the effects of large amounts, or of combining it with other stimulants, are not fully known. It may also interact with some medications. Methylsynephrine is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Methylsynephrine interact with any medications?

Possible interactions include: Caffeine and other stimulants (synephrine, deterenol, yohimbine and similar pre-workout ingredients): products have combined up to 4 prohibited stimulants, mixes never tested in humans, and the effects of combining methylsynephrine with other stimulants are not fully known. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Methylsynephrine?

NutraSmarts rates the evidence for Methylsynephrine as Preliminary (1 out of 5). It is backed by 8 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies. For a drug or research chemical, this rating does not mean it is suitable for self-use.

References(16 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Test Anal. 2017;9(1):135-142. doi: 10.1002/dta.1976.PubMedUsed to support: Analysis of 27 US supplement brands labeled as containing methylsynephrine: oxilofrine was present in 14 (52%) at 0.0003 to 75 mg per serving, 6 of the 14 held pharmaceutical or greater doses, and label directions allowed up to 250 mg a day. States that oxilofrine is prescribed at 16 to 40 mg to stimulate the heart and raise blood pressure, has never been approved in the US as a drug or supplement, that athletes have been banned after testing positive, and that one brand containing it was linked to vomiting, agitation and cardiac arrest.
  2. Pawar RS, Sagi S, Leontyev D. Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS. Drug Test Anal. 2020;12(9):1241-1251. doi: 10.1002/dta.2871.PubMedUsed to support: FDA laboratory analysis of 59 US products labeled as containing bitter orange or its amines. The synthetic amine methylsynephrine, whose effects in humans the authors describe as not known, was detected in 6 products at up to 240 mg per daily serving; the authors state that methylsynephrine is not permitted in dietary supplements.
  3. Cohen PA, Travis JC, Vanhee C, Ohana D, Venhuis BJ. Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA) and higenamine. Clin Toxicol (Phila). 2021;59(11):975-981. doi: 10.1080/15563650.2021.1894333.PubMedUsed to support: Analysis of 17 US supplement brands labeled as containing deterenol: 9 prohibited stimulants were found, with as many as 4 in one product, including oxilofrine at 18 to 55 mg per recommended serving. The authors conclude these stimulant cocktails have never been tested in humans and their safety is unknown. A correction was published in 2022 (Clin Toxicol 60(6):671).
  4. Duiven E, van Loon LJC, Spruijt L, Koert W, de Hon OM. Undeclared Doping Substances are Highly Prevalent in Commercial Sports Nutrition Supplements. J Sports Sci Med. 2021;20(2):328-338. doi: 10.52082/jssm.2021.328.PubMedUsed to support: Doping Authority Netherlands study of 66 high-risk sports supplements bought from Dutch web shops: 25 (38%) contained undeclared doping substances, including high levels of the stimulant oxilofrine, and some products could cause unintentional doping violations.
  5. Venhuis B, Keizers P, van Riel A, de Kaste D. A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug Test Anal. 2014;6(6):578-81. doi: 10.1002/dta.1664.PubMedUsed to support: The Dutch supplement Dexaprine was removed from the market after reports to the Dutch Poisons Information Center of nausea, agitation, fast heart rate and palpitations after as little as half a tablet, and one cardiac arrest. Tablets from 4 patients contained synephrine, oxilofrine, deterenol, yohimbine, caffeine and theophylline. A multi-ingredient product, so the role of oxilofrine alone is unknown.
  6. Rickli A, Hoener MC, Liechti ME. Pharmacological profiles of compounds in preworkout supplements ("boosters"). Eur J Pharmacol. 2019;859:172515. doi: 10.1016/j.ejphar.2019.172515.PubMedUsed to support: In vitro study in human cells expressing monoamine transporters: methylsynephrine, like several other pre-workout phenethylamines, inhibited the noradrenaline transporter and less potently the dopamine transporter, similar to D-amphetamine; none of the compounds blocked the serotonin transporter. The authors conclude such products may contain substances with mainly noradrenergic, amphetamine-type properties. Cell work only.
  7. Verho M, Malerczyk V, Kauert G, Lorenz H. Dose linearity and relative bioavailability testing of oxilofrine, a sympathicomimetic drug, in healthy volunteers. Int J Clin Pharmacol Res. 1988;8(3):211-5..PubMedUsed to support: Open Latin-square study in 12 healthy men given single oral doses of 16, 32 and 64 mg oxilofrine tablets and 16 mg drops: median peak plasma levels were 11.4, 31.4 and 122.9 ng/mL for the tablets, reached within 0.7 to 1.7 hours; exposure rose faster than the dose, suggesting saturable first-pass metabolism, and about 50% of the dose appeared in urine. No side effects were reported. First author from Hoechst AG clinical research.
  8. Kauert G, Angermann C, Lex H, Spes C. Clinical pharmacokinetics after a single oral dose of oxilofrine. Int J Clin Pharmacol Res. 1988;8(5):307-14..PubMedUsed to support: Study in 8 healthy volunteers given a single 120 mg oral dose of oxilofrine: heart rate and mean arterial pressure were unchanged, peripheral resistance fell on average, systolic pressure rose by up to 13.8% and diastolic fell by up to 8.8%, and left ventricular fractional shortening rose 20.9% (velocity 29.5%), a long-lasting positive inotropic effect correlated with plasma levels (r = 0.981). A second plasma peak at 2 to 3 hours suggested enterohepatic reabsorption.
  9. Pohl K, Kriech W. [Therapy of orthostatic disorders of cardiovascular regulation. Placebo controlled double-blind study with oxilofrine]. Fortschr Med. 1991;109(33):685-8. German..PubMedUsed to support: Double-blind trial in 60 patients with orthostatic circulatory regulation disorders (30 oxilofrine, 30 placebo, 2 weeks): the primary Schellong test measure rose 48% with oxilofrine versus 20.8% with placebo, a significant difference, and standing systolic pressure held steady with the drug but fell with placebo. Listed affiliation includes Albert-Roussel-Pharma GmbH. Drug research, not supplement use.
  10. Logan IC, Witham MD. Efficacy of treatments for orthostatic hypotension: a systematic review. Age Ageing. 2012;41(5):587-94. doi: 10.1093/ageing/afs061.PubMedUsed to support: Systematic review of 36 randomized placebo-controlled trials of 21 interventions for orthostatic hypotension; most trials were poor quality with a high risk of bias and no meta-analysis was possible. Oxilofrine was among the treatments that improved the postural blood pressure drop. Drug evidence in patients only.
  11. Rapin JR, Jacquot C. [Effects of oxilofrine on the activity of the sympathetic nervous system (author's transl)]. Arzneimittelforschung. 1980;30(7):1077-9. German..PubMedUsed to support: Isolated rat heart and spleen tissue plus in vivo experiments on heart noradrenaline synthesis: oxilofrine strongly inhibited noradrenaline storage in the heart and released noradrenaline from storage, mainly newly synthesized noradrenaline, while speeding noradrenaline production, raising transmitter levels near the receptors. Animal and tissue work only.
  12. US Food and Drug Administration. Methylsynephrine in Dietary Supplements. US Food and Drug Administration. 2023;Information on select dietary supplement ingredients; content current as of 02/22/2023. Accessed 2026..SourceUsed to support: Not PubMed-indexed; official FDA page. States that methylsynephrine, also known as oxilofrine and p-hydroxyephedrine, does not meet the statutory definition of a dietary ingredient, so dietary supplements that declare it as a dietary ingredient are misbranded, and refers to FDA's March 2016 action.
  13. US Food and Drug Administration. Recent FDA Action on Dietary Supplements for Which the Product Labeling Lists Methylsynephrine as a Dietary Ingredient. US Food and Drug Administration. 2016;Constituent update dated March 31, 2016. Accessed 2026..SourceUsed to support: Not PubMed-indexed; FDA announcement. On March 31, 2016 FDA issued warning letters to 7 companies covering 8 products whose labels list methylsynephrine as a dietary ingredient, stating that it does not fit any category in the legal definition of a dietary ingredient, which renders such products misbranded; companies had 15 business days to respond.
  14. US Food and Drug Administration. Warning Letter: Total Body Nutrition, MARCS-CMS 526219. US Food and Drug Administration. 2017;Warning letter dated September 28, 2017. Accessed 2026..SourceUsed to support: Not PubMed-indexed; FDA enforcement letter. States that the product Shredder is misbranded under section 403(a)(1) because its label lists methylsynephrine as a dietary ingredient although methylsynephrine does not meet the definition of a dietary ingredient under section 201(ff)(1), and notes FDA had told the firm this in a March 31, 2016 warning letter.
  15. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. World Anti-Doping Agency. 2026;Section S6.B Specified Stimulants; in effect from 1 January 2026. Copy hosted by the Czech National Sports Agency (Narodni sportovni agentura), accessed 2026..SourceUsed to support: Not PubMed-indexed; official anti-doping list. Oxilofrine (methylsynephrine) is named under S6.B Specified Stimulants, prohibited in competition, alongside octopamine and midodrine. Synephrine is listed instead in the 2026 Monitoring Program and is not considered a prohibited substance.
  16. Operation Supplement Safety (OPSS), US Department of Defense. Methylsynephrine: An Illegal Ingredient. Operation Supplement Safety. 2022;Article updated 7 March 2022. Accessed 2026..SourceUsed to support: Not PubMed-indexed; US Department of Defense dietary supplement safety resource. States that methylsynephrine (oxilofrine, p-hydroxyephedrine) is on the DoD Prohibited Dietary Supplement Ingredients list, is prohibited in sport, is an approved drug in some countries but not the US, is a stimulant that increases blood pressure and affects heart rate, that the effects of large amounts or of combining it with other stimulants are not fully known, and that one product containing it with other stimulants was linked to nausea, vomiting, agitation, fast heart rate, chest pain and cardiac arrest.