Hordenine is a naturally occurring substance found in several plants, including barley (from which its name originates: Hordeum vulgare), seaweeds, Aconitum tanguticum (Maxim.) Stapf, Senecio scandens, Coryphantha ramillosa, and Citrus aurantium (bitter orange). Hordenine also can be made in a laboratory (that is, as a synthetic chemical). Both natural and synthetic hordenine might promote stimulant effects.

Products containing hordenine are considered “adulterated,” and the safety of hordenine is unknown.

Hordenine is structurally similar to other natural phenethylamines (which act to stimulate the body), such as N-methyltyramine and synephrine, and it appears to be structurally related to ephedrine. In fact, when ephedra-containing products were removed from the dietary supplement market due to safety concerns, other stimulant substances (including hordenine) began to emerge as ingredients in dietary supplement products marketed for weight loss and athletic performance.

The U.S. Food & Drug Administration (FDA) recently determined hordenine to be a “new dietary ingredient (NDI) for which an NDI notification is required and has not yet been submitted.” Therefore, any product containing hordenine is considered “adulterated.”

What does the science say?

Hordenine is possibly unsafe when taken by mouth and might cause stimulant side effects such as rapid heart rate and high blood pressure. Most studies showing these effects were done with animals, and limited human studies are available to date. The latest studies analyzing products that list hordenine as an ingredient show that such products sometimes contain more hordenine than reported on product labels, while others can contain additional substances (either listed or not shown on the labels) not approved for use in dietary supplements.

How can I watch out for this ingredient?

Although FDA guidelines require manufacturers to list common names of an ingredient, you should be aware of other names used so you can avoid adulterated hordenine products. Some names that might appear on a product label instead of “hordenine” include:

  • anhaline
  • eremursine
  • N,N-dimethyltyramine
  • peyocactine
  • p-hydroxy-N,N-dimethylphenethylamine
  • 4-[2-(dimethylamino)ethyl]phenol
  • 2-(4-hydroxyphenyl)N,Ndimethyl-
  • ethylamine
  • cactine
  • ordenina
  • ordenine
  • N,N-dimethyl-4-hydroxy-beta-phenethylamine

Hordenine is on the National Collegiate Athletic Association’s (NCAA) list of banned substances. In addition, hordenine might register on an initial urine screening test for amphetamines or opioids, but it will not cause a positive result on a confirmation drug test.

Bottom line

Products containing hordenine are considered “adulterated” because it is a new dietary ingredient that hasn’t been submitted to FDA to establish its safety. It is unknown how they might affect your readiness or health.

 

Updated 22 November 2021

References

Crawford, C., Wang, Y.-H., Avula, B., Bae, J.-Y., Khan, I. A., & Deuster, P. A. (2020). The scoop on brain health dietary supplement products containing huperzine A. Clinical Toxicology, 58(10), 991–996. doi:10.1080/15563650.2020.1713337

FDA. (1988). FDA Poisonous Plant Database: Hordenine.   Retrieved 12 May 2021 from https://www.cfsanappsexternal.fda.gov/scripts/plantox/detail.cfm?id=12465

FDA. (2020). Fusion Health and Vitality issues voluntary nationwide recall of Core Essential Nutrients and Immune Boost sublingual vitamin D3 due to the unapproved use of a food additive and unapproved marketing statements.   Retrieved 12 May 2021 from https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/fusion-health-and-vitality-issues-voluntary-nationwide-recall-core-essential-nutrients-and-immune

FDA. (2021a). Dietary Supplement Ingredient Advisory List. Retrieved 22 November 2021 from https://www.fda.gov/food/dietary-supplement-products-ingredients/dietary-supplement-ingredient-advisory-list

FDA. (2021b). Warning Letter: 1st Phorm LLC. Retrieved 22 November 2021 from https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/1st-phorm-llc-613715-07292021

Hapke, H. J., & Strathmann, W. (1995). Pharmacological effects of hordenine. Deutsche Tierärztliche Wochenschrift, 102(6), 228–232.  Retrieved from https://pubmed.ncbi.nlm.nih.gov/8582256/

Hintz, H. F. (1988). Hordenine. Equine Practice, 10(2), 17.

Hoffman, J. R., Kang, J., Ratamess, N. A., Rashti, S. L., Tranchina, C. P., & Faigenbaum, A. D. (2009). Thermogenic effect of an acute ingestion of a weight loss supplement. Journal of the International Society of Sports Nutrition, 6, article 1. doi:10.1186/1550-2783-6-1

Jitomir, J., Nassar, E., Culbertson, J., Moreillon, J., Buford, T., Hudson, G., . . . Willoughby, D. S. (2008). The acute effects of the thermogenic supplement Meltdown on energy expenditure, fat oxidation, and hemodynamic responses in young, healthy males. Journal of the International Society of Sports Nutrition, 5(1), article 23. doi:10.1186/1550-2783-5-23

Ma, J., Wang, S., Huang, X., Geng, P., Wen, C., Zhou, Y., . . . Wang, X. (2015). Validated UPLC–MS/MS method for determination of hordenine in rat plasma and its application to pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis, 111, 131–137. doi:10.1016/j.jpba.2015.03.032

NCAA. (2021). NCAA Banned Substances. Retrieved 22 November 2021 from https://www.ncaa.org/2015-16-ncaa-banned-drugs

Pawar, R. S., Sagi, S., & Leontyev, D. (2020). Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC–MS/MS. Drug Testing and Analysis, 12(9), 1241≠1251. doi:10.1002/dta.2871

Sobiech, M., Giebułtowicz, J., & Luliński, P. (2020). Theoretical and experimental proof for selective response of imprinted sorbent – analysis of hordenine in human urine. Journal of Chromatography A, 1613, article 460677. doi:10.1016/j.chroma.2019.460677

Sommer, T., Dlugash, G., Hübner, H., Gmeiner, P., & Pischetsrieder, M. (2019). Monitoring of the dopamine D2 receptor agonists hordenine and N-methyltyramine during the brewing process and in commercial beer samples. Food Chemistry, 276, 745753. doi:10.1016/j.foodchem.2018.10.067

Sommer, T., Göen, T., Budnik, N., & Pischetsrieder, M. (2020). Absorption, biokinetics, and metabolism of the dopamine D2 receptor agonist hordenine (N,N-dimethyltyramine) after beer consumption in humans. Journal of Agricultural and Food Chemistry, 68(7), 1998–2006. doi:10.1021/acs.jafc.9b06029

Stohs, S. J., Shara, M., & Ray, S. D. (2020). p‐Synephrine, ephedrine, p‐octopamine and m‐synephrine: Comparative mechanistic, physiological and pharmacological properties. Phytotherapy Research, 34(8), 1838–1846. doi:10.1002/ptr.6649