The amine hypothesis

high-protein diets and behavioural problems in horses

Christine King  BVSc, MANZCVS (equine), MVetClinStud

Table of Contents

Introduction

1. The problematic behaviour

2. The problematic pasture

3. The problematic weather

4. The amine hypothesis

5. The (failed) amine–laminitis hypothesis

6. The amine–behaviour hypothesis

7. What do we know?

8. What can we do?

Full reference list

Read on...

© Christine M. King, 2026. All rights reserved.

First published on 31 August, 2026. Last updated 08 September, 2026.

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Table 1. Concentrations of 15 amines in the caecum and colon of 10 horses fed hay and sampled in the winter.[6]

These data are from 10 horses fed only hay and sampled in the winter. The same amines are found in horses on grass in the winter and spring/summer, some at much higher concentrations than in hay-fed horses (Figure 4).

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.

☐ winter hay

☒ winter grass

■ spring/summer grass

Eleven of the 15 amines measured in the horse's hindgut were present in significantly higher concentrations in the colon than in the caecum (the first part of the horse's hindgut).

Microbial fermentation of food begins in the horse's stomach and continues in the small intestine, but it dramatically ramps up in the caecum, and reaches its peak in the colon.

For example, horses get up to 80% of their daily energy needs for maintenance (their walking-around calories) from the short-chain fatty acids (SCFA) produced by the microbial fermentation of dietary fibre in the hindgut. Whereas 30% of those SCFAs are generated by the microbes in the caecum, 50% are made in the colon.[7]

Amines and laminitis

Given that several amines have sympathomimetic (adrenaline-like) properties, four of these hindgut amines were examined for their potential role in laminitis. They are the four amines circled in Figure 4 (above): tryptamine, tyramine, phenylethylamine (PEA), and isoamylamine.

In the lab. Experimentally, tryptamine, tyramine, and PEA each caused concentration-dependent constriction of veins and arteries from the horse's foot — that is, in isolated blood vessels studied in the lab (in vitro). The higher the concentration of amine, the greater the amount of blood vessel constriction.[8]

The thresholds for a vasoconstrictive effect (i.e., the lowest amine concentration that caused any measurable constriction) ranged from a low of 6.8 nM (nanomoles) for tryptamine to a high of around 2 µM (micromoles) for tyramine and PEA (Figure 5).

By the way, 1 nanomole is one-thousandth (0.001) of a micromole, so tryptamine was almost 300 times more potent than the other two.

Figure 5. Vasoconstrictive effects of tryptamine, tyramine, and phenylethylamine on equine digital veins ( ▲) and arteries ( ◼ ︎) in vitro (n=6 horses). Results are expressed as a percentage of the response obtained by incubating the vessels in depolarizing Krebs solution (DKS). Each datapoint represents the mean ± standard error of the mean.[8]

Worth noting for later, isoamylamine and isobutylamine were also studied. They failed to cause vasoconstriction at the maximum concentration tested.

In the horse. In a related in vivo (live horse) study, intravenous infusion of tryptamine (1.6 µg/kg/min IV) decreased blood flow in the digital arteries by an average of 29% ± 21%, as measured by Doppler ultrasound.[9]

So, tryptamine caused modest vasoconstriction, to the tune of around 30%, give or take 20%. (By the way, that's a lot of individual variation for just six horses: 8–50%. )

In that same study, intravenous infusion of PEA (2.13 ug/kg/min IV) decreased digital arterial blood flow by an average of 18% ± 17%. So, by around 20%, give or take 17%. (Again, a huge amount of individual variation: 1.7–35.1%).

Are these effect sizes large enough to trigger laminitis in a natural setting? Apparently not…

Ultimately, this initially-promising hypothesis was a bust, because what was evident in the lab and in a carefully controlled experimental setting did not hold true in the field:

While blood (plasma) amine concentrations in ponies on pasture significantly increased between winter and spring, they did not exceed the experimental thresholds for constriction of blood vessels in the hoof, even in laminitis-prone ponies on spring pasture.[10] I'll discuss that particular study in the next section.

But the (failed) amine-laminitis research has proven useful, as it provided some data I could comb through for clues that might support an amine–behaviour hypothesis.

That's next.

. . .

References

[6] Bailey SR, Marr CM, Elliott J. Identification and quantification of amines in the equine caecum. Research in Veterinary Science, 2003; 74: 113–118.

[7] Anon. Energy. In Nutrient Requirements of Horses, 6th revised edition. National Research Council (NRC). The National Academies Press, Washington DC, 2007; p. 6.

[8] Elliott J, Berhane Y, Bailey SR. Effects of monoamines formed in the cecum of horses on equine digital blood vessels and platelets. American Journal of Veterinary Research, 2003; 64(9): 1124–1131.

[9] Bailey SR, Menzies-Gow NJ, Marr CM, et al. The effects of vasoactive amines found in the equine hindgut on digital blood flow in the normal horse. Equine Veterinary Journal, 2004; 36(3): 267–272.

[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.