animal health consulting
The amine hypothesis
high-protein diets and behavioural problems in horses
Christine King BVSc, MANZCVS (equine), MVetClinStud
What do we know?
3. Many different amines are produced in the horse's hindgut.
I briefly discussed these studies in Part 5, The (failed) amine-laminitis hypothesis.
Thus far, 15 trace amines have been identified in the horse's caecum and colon in concentrations worthy of consideration. Four have been further studied for their potential role in laminitis: tryptamine, tyramine, phenylethylamine (PEA), and isoamylamine.
. . .
4. Amines in the hindgut are absorbed into the bloodstream.
Although the concentrations of amines in the bloodstream are much lower than those in the caecum and colon, measurable amounts of food- and gut-derived amines cross the intestinal barrier in horses. I'll show you that in a bit.
Some of these amines, notably tryptamine and PEA, readily cross cellular barriers, including the intestinal barrier and the blood-brain barrier.[18] Other trace amines of interest, simply because they have been studied at least a little in horses, also appear to readily cross the intestinal barrier into the bloodstream.
By the way, the subtitle of reference [18] is this striking promise: linking microbial fitness and host neurochemical communication.
It's a very dense review paper, but it connected a lot of dots for me. The 'microbial fitness' part is about how the gut microbes produce trace amines as a protective measure in an acidic environment. The 'host neurochemical communication' part is about how gut-derived trace amines affect our neurochemistry. But I digress.
High-NSC diets and their associated hindgut acidity compromise the intestinal barrier (↑ intestinal permeability), a situation commonly known as 'leaky gut'. But that's not actually necessary in order for food- and gut-derived amines to pass from the hindgut into the bloodstream — although I'm sure a leaky gut speeds the passage of amines across the intestinal barrier. It's the hindgut acidity that is the important piece here, in both the explanation for the abnormal behaviour and what, thus far, has been an effective solution. More on that in the final section, on what we can do about it.
. . .
5. There is a seasonal effect: caecal and plasma amines in horses are higher in the spring than in the winter.
Here's a quick reminder of the study that showed higher concentrations of several amines in the caecum of horses on grass compared with those on a hay-only diet.[6]
Table of Contents
5. The (failed) amine–laminitis hypothesis
6. The amine–behaviour hypothesis
7. What do we know?
© Christine M. King, 2026. All rights reserved.
First published on 31 August, 2026. Last updated 08 September, 2026.
This concludes what we do know. Before I discuss what we can do about all this, I want to briefly cover what we don't know yet.
Click on the 'Read on...' link below the Table of Contents.
. . .
Reference
[6] Bailey SR, Marr CM, Elliott J. Identification and quantification of amines in the equine caecum. Research in Veterinary Science, 2003; 74: 113–118.
[10] Bailey SR, Katz LM, Berhane Y, et al. Seasonal changes in plasma concentrations of cecum-derived amines in clinically normal ponies and ponies predisposed to laminitis. American Journal of Veterinary Research, 2003; 64(9): 1132–1138.
[18] Rahmdel S, Luqman A, Götz F. Microbiota-derived aromatic amino acid decarboxylases: linking microbial fitness and host neurochemical communication. mBio, 2025; 16(11): 1–12.
Note these two things in particular:
1. Plasma amines were generally higher in spring than in winter, for both groups of ponies.
That is the broad brushstroke; the take-home message. However,…
2. There was tremendous individual variation among ponies, even within the same group and season.
Even in the winter, there was a substantial amount of individual variation among ponies in the same group, on the same pasture, particularly for PEA and isoamylamine.
Some ponies had plasma amine concentrations in the spring that were dramatically higher than the rest of their group. I wish we were told if these were the same two or three ponies in each graph. Alas, we are not told, although I suspect that they were.
And in perhaps the most striking example of individual responses to the same pasture conditions, plasma tyramine, PEA, and isoamylamine concentrations decreased from winter to spring in some ponies, while they increased in others, and remained unchanged in the rest. Are the same ponies in each graph having the same response (increase, decrease, or no change)? We're not told, but probably so.
. . .
As for tryptamine, the potentially hallucinogenic amine which readily crosses the blood-brain barrier, there are two things to note:
1. Plasma concentrations were negligible in the winter, and then they virtually 'exploded' in the spring.
In the Control group alone (the healthy ponies), there was an 111-fold increase in median tryptamine concentration between winter and spring, whereas for PEA there was only a 2-fold increase.
2. There was a great deal of individual variation among ponies in the spring.
In both groups, there was at least a 20-fold difference between the highest and lowest values in the group.
. . .
I keep stressing and illustrating the tremendous range of individual responses to the same diet because it matters.
It explains why some horses have problems on lush grass while others don't.
It explains why the physical and behavioural problems some horses have on lush grass are really to be seen on a spectrum, rather than being binary: on/off, yes/no, present/absent.
And it explains why the problems in these horses may be intermittent, inconsistent, or episodic: because weather and pasture conditions are never the same from one month, or even one day, to the next.
. . .
Figure 4. Selected amine concentrations in the caecum of horses fed hay in winter (☐), winter grass (☒), or spring/summer grass (■), 10 horses each group. Bars and whiskers represent mean and standard error of the mean. Letters represent significant difference compared with (a) winter hay, and (b) winter grass.[6] Circled are the four amines that have also been measured in the horse's bloodstream. Discussed here.
And now here is the study which showed that the four circled amines are higher in the bloodstream in the spring than in the winter.[10]
This UK study involved 42 ponies on pasture year-round: 22 healthy ponies (Control group) and 20 ponies who had a history of pasture-associated laminitis (Laminitis group), although none of the ponies had an episode of laminitis during the study year.
Plasma amines were compared in the winter and the spring, as spring is typically the season in which laminitis risk is the greatest. Unfortunately, the study did not report on plasma amine concentrations in the other two seasons.
But here's what happened between winter and spring, in four graphs:
Figure 9 (a). Plasma tryptamine concentrations in the winter and spring in 42 ponies on pasture, 22 healthy ponies (Control) and 20 laminitis-prone ponies (Laminitis). NS, no significant difference between groups. *** Significant difference between seasons (P < 0.001).[10]
Figure 9 (b). Plasma tyramine concentrations in the winter and spring in 42 ponies on pasture, 22 healthy ponies (Control) and 20 laminitis-prone ponies (Laminitis). NS, no significant difference between groups/seasons).[10]
Figure 9 (c). Plasma phenylethylamine (PEA) concentrations in the winter and spring in 42 ponies on pasture, 22 healthy ponies (Control) and 20 laminitis-prone ponies (Laminitis). NS, no significant difference between groups. **, *** Significant difference between seasons (** P = 0.01 and *** P < 0.001).[10]
Figure 9 (d). Plasma isoamylamine concentrations in the winter and spring in 42 ponies on pasture, 22 healthy ponies (Control) and 20 laminitis-prone ponies (Laminitis). NS, no significant difference between groups. **, *** Significant difference between seasons (** P = 0.01 and *** P < 0.001).[10]