animal health consulting

The amine hypothesis

Amines are small, organic molecules that contain nitrogen. They typically have names ending in -amine, such as tryptamine and tyramine. The ones we're interested in are closely related to some well-known neurotransmitters, such as dopamine, serotonin (aka 5-hydroxytryptamine), and noradrenaline (aka norepinephrine).

The body produces amines naturally, but in miniscule amounts (e.g., nanograms per gram of brain tissue).[4] That's why they're referred to as 'trace amines' in research circles; they're present in only tiny or trace amounts. In these normally low tissue concentrations, they act as neuromodulators, affecting the activity or expression of the classical neurotransmitters.[4]

The amines I'm about to discuss in relation to horses make the nervous system more sensitive to all sorts of stimuli. In this way, they act as central nervous system stimulants.

At low (physiological) concentrations, they have effects similar to adrenaline, hence their scientific label, sympathomimetics — they mimic (or more accurately, exaggerate) the effects of sympathetic nervous system stimulation, the fight-or-flight response of an adrenaline-fueled body.

Oh, that makes so much sense when I consider how these horses look and act during one of these episodes…

At high (pharmacological) concentrations, these amines have amphetamine-like effects. Amphetamines; “speed”! And at least one, tryptamine, can have hallucinogenic effects. In fact, psilocybin (from “magic mushrooms”) is a tryptamine derivative.

Now the horses' abnormal behaviour makes even more sense!

So, that's a very short primer on the amines of interest and their potential effects on the horse's brain. I should also note that trace amine receptors are present in many different tissues throughout the body, including the spinal cord, heart, kidneys, spleen, pancreas, fat, testes (testicles), white blood cells, respiratory tract (nasal passages, trachea [windpipe], lungs) — and, particularly in relation to the gelding I see from my window, the stomach, intestines, and muscles.[5]

Food- and gut-derived amines

As for where these amines come from, they are naturally found in food and they are produced by our gut microbes, as well as by our own cells.

It's the microbially produced or gut-derived amines that I'm most interested in, because there is clearly a dietary element to these horses' abnormal behaviour.

Food-derived amines in human diets mostly come from fermented foods, such as aged cheese, cured meat, wine, and chocolate. In comparison, the horse's diet should be fairly low in amines.

I say "should" because I just don't know. As far as I'm aware, no-one has looked at food-derived amines in horses yet.

Does haylage — fermented grass or lucerne (alfalfa) that would otherwise be dried and baled as hay — contain more amines than ordinary hay? Probably.

Is that a problem? Who knows. And it may depend a great deal on the crude protein content of the grass or legume used to make the haylage.

Does the processing of high-protein feedstuffs, such as soybeans, lupins, and fava/faba beans, increase their amine content? Probably.

Is that a problem? Who knows, although one of the first things we did when we got the May pasture results (29.3% CP) was to dramatically decrease the three high-protein supplemental feeds the horses were on — a grain-free sporthorse ration containing soybeans, lupins, and lucerne; coconut meal; and lucerne hay— all around 20% CP. Those supplemental feeds were being used because the protein content of the summer hay was so low (6% CP).

Cutting way down on these high-protein feeds did help, although it didn't stop the episodes of abnormal behaviour. They were less frequent and extreme, but they still recurred.

Same with the addition of zeolite, an inert clay powder I hoped would mop up the potentially harmful byproducts of microbial fermentation in the hindgut. It helped, too, but it didn't completely stop the episodes. That's because the horses remained on the pasture, and we later learned that its protein content remained high through August (26.8% CP).

When I sat down to estimate how much surplus protein the horses were getting from these autumn and winter pastures, the result astonished me: they were consuming an estimated 2 kg/day of surplus protein — that is, above and beyond their daily protein needs for maintenance. I'll go through the maths a bit later, in case you're curious, although you can always skip over it if maths make you cry in exasperation. (I am mathematically challenged myself, so I do understand ☺︎.)

So, under what conditions do food- and gut-derived amines increase to the point of causing physical or behavioural problems in horses?

I have a pretty good idea now, but I don't know for sure. Amines and behaviour have not yet been studied in horses. There is, however, a small handful of studies on gut-derived amines in horses, in relation to laminitis risk. So, let's start there.

. . .

References

[4] Berry MD. Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. Journal of Neurochemistry, 2004; 90: 257–271.

[5] Gainetdinov RR, Hoener MC, Berry MD. Trace amines and their receptors. Pharmacological Reviews, 2018; 70: 549–620.