Hordenine is a naturally-occurring atypical stimulant that is found in barley, bitter orange and cacti such as Echinopsis candicans. Sometimes it is found in weight loss or athletic performance enhancement supplements in larger amounts and sometimes it is found in fake “bitter orange extracts”, which may actually be a mixture of different synthetic phenylethylamine stimulants [1]. Is hordenine a good enhancer of coffee or a good alternative to it? Indeed, in the first place it is not very well researched. It is one of the many atypical minor phenylethylamine stimulants that is considered reasonably safe in smaller doses. In higher doses, is also sold as a supplement for weight loss or athletic performance enhancer. Are there any concerns?

Hordenine is no doubt bioactive. It is a relatively poor but selective inhibitor of monoamine oxidase B that breaks down dopamine [2] and phenylethylamine (PEA), prolonging their effect in the brain, heart and kidneys. While it does not mimic noradrenaline itself, it inhibits the removal of noradrenaline from synapses, and thus increases noradrenergic tone [2]. Therefore, it is a stimulant. Inhibiting breakdown of dopamine might reduce oxidative stress and might be useful for some neural conditions (mood disorders, Parkinson’s disease) and potentially disadvantageous in others (schizophrenia, anxiety disorders). Inhibition of noradrenaline uptake may be useful in the context of mood and attention disorders while it is reasonable to speculate that it may be dangerous in the context of hypertension and related diseases as well as anxiety disorders. The combined effect of these with other stimulants with different mechanisms may be greater than sum of their parts, and thus more potent as well as more dangerous.

It has been found that hordenine blocks synthesis of melanin, which is a molecule that protects the skin from the damaging effects of the sunlight [3]. The paper discussed that this property of hordenine might have potential pertinent to hyperpigmentation disorders. In the same time, it seems wise to consider that inhibition of normal tanning might increase the risk of skin cancer in some contexts.

An animal study has found that hordenine may be a kidney-friendly substance in mice with chemically induced diabetes. More specifically, hordenine reduced inflammation mediators IL-1beta and IL-6 as well as (in this context) harmful tissue remodeling enzyme MMP-9 [4]. Reduction of oxidative stress indicates normalization of haywire metabolism in the kidneys (ROS). While this is just one study made in animals, it is of great interest because it is not so easy to find molecules that are beneficial for kidneys (or liver).

High doses of hordenine have been investigated in the horse [5]. The responses of the horses were flehmen response (expression of intestinal discomfort, probably), defecation within 60 seconds, respiratory distress and doubling of heart rate. These responses to 2 mg/kg injection were transient and animals biological signs returned to normal within 30 minutes. When the same dose was given to animals orally, no such responses were recorded; the concentration of hordenine returned to baseline within 24 h.

Hordenine reduces the disease causing capacity of certain Pseudomonas aeruginosa or Serratia marcescens strains [6,7]. These bacteria are not so often found from healthy persons. It is unknown whether hordenine has any useful or harmful effect on the healthy persons’ beneficial bacteria that are mostly quite different from these two species.

Hordenine has weak dopamine D2 agonist properties. Consumption of beer is insufficient source of hordenine for this to become pertinent but higher doses found in food supplements with high concentrations might [8]. D2 receptor is pertinent for goal maintenance during mental tasks [9], less receptors are linked to better working memory and task switching.

While increased dopaminergic tone via MAO B inhibition might be beneficial for cognitive enhancement, substantial activation of D2 receptors might reduce cognitive performance, instead. Therefore, while it is clear that hordenine is a cardiovascular, nervous system and metabolism stimulant, nootropic properties are debatable – while it might me mildly nootroopic, the opposite may be true, instead.

 

[1] https://pubmed.ncbi.nlm.nih.gov/32497396/
[2] https://pubmed.ncbi.nlm.nih.gov/2570842/
[3] https://pubmed.ncbi.nlm.nih.gov/23768344/
[4] https://pubmed.ncbi.nlm.nih.gov/29775900/
[5] https://pubmed.ncbi.nlm.nih.gov/2269269
[6] https://pubmed.ncbi.nlm.nih.gov/29353476/
[7] https://pubmed.ncbi.nlm.nih.gov/30609368/
[8] https://pubmed.ncbi.nlm.nih.gov/31984737/
[9] https://pubmed.ncbi.nlm.nih.gov/30125286//