In a previous newsletter, we discussed the role of protein in the equine diet (available here). We often think of proteins simply as the building blocks for muscle, hooves, and enzymes. However, individual amino acids can actually act as potent signaling molecules. This is one of the most fascinating areas of modern equine nutrition.
◆︎ How do amino acids act as signaling molecules?
Specific amino acids act as signaling molecules through a variety of mechanisms, including:
☛ Binding directly to cellular receptors to trigger a response.
☛ Acting as epigenetic switches, turning the genes that create other signaling molecules “ON” or “OFF.”
☛ Modulating the body's internal inflammatory pathways.

Real-Life Applications in Your Horse:
◆︎ N-Acetyl Cysteine (NAC): NAC is a highly bioavailable precursor to cysteine, which is the rate-limiting amino acid needed to create glutathione—the horse's master intracellular antioxidant. It actively dampens inflammatory pathways.
➡ Respiratory Inflammation: Highly effective for horses struggling with dust, pollen, allergens, barn cough, or wildfire smoke.
➡ Thinning Mucus: When a horse is struggling to breathe, it is not unusual for thick mucus to be present in the trachea. NAC physically breaks the disulfide bonds in mucus, thinning it out so the horse can clear its airways.
➡ Exercise Recovery: Dampens the inflammatory pathways triggered by intense exercise.
➡ Liver Support: The liver depends on massive amounts of glutathione to detoxify the blood. NAC provides one of the building blocks the liver needs to create it.

◆︎ Acetyl-L-Carnitine (ALCAR): ALCAR sends a signal to the cells to build brand new mitochondria (the powerhouse of the cell). Because ALCAR works at the level of transcription, it can take 6 to 8 weeks of consistent use to see noticeable effects.
☛ Geriatric Muscle Support: By increasing the number of mitochondria, ALCAR helps older horses suffering from muscle loss regain better muscle function and combat geriatric fatigue. This is especially important for horses with muscle loss due to PPID.
☛ Athletic Stamina: Horses in active work can significantly increase their stamina by increasing the number of mitochondria in their muscles.
☛ Insulin Sensitivity: Expanding the mitochondrial network helps regulate glucose utilization by the muscles, which may improve overall insulin sensitivity in horses with insulin resistance.
☛ Neuropathic Pain: By affecting the nervous system, ALCAR may also be helpful as an adjunctive support for horses dealing with chronic nerve pain.

◆︎ L-Carnitine: L-Carnitine is an amino acid that enhances the transport of long-chain fatty acids directly into the mitochondria. This allows the cell to use fats for fuel instead of sugars. This ability to easily utilize fats is critical for overweight horses, horses with PSSM, or horses taking SGLT2 inhibitors.
◆︎ Leucine: Leucine is a potent signaling molecule for the creation of new muscle. However, there is a catch: if your horse is on a forage-only diet and you supplement only leucine, the horse will still lack the limiting amino acids needed to build muscle. To be most effective, the primary limiting amino acids (lysine, methionine, and threonine) should also be supplemented in adequate amounts. Supplements like Top 3 Aminos can provide those limiting amino acids, while products like Top 4 Aminos provide the limiting amino acids and the leucine signal.
◆︎ Arginine Alpha-Ketoglutarate (AAKG):This dual-action molecule is incredibly useful for horses laid up with a tissue injury (like a torn tendon). The alpha-ketoglutarate portion of the molecule signals the body to prevent muscle wasting during stall rest. The arginine portion promotes new blood vessel formation and collagen synthesis to repair the damaged tissue.

◆︎ Parting Thoughts:
There are many more amino acids that act as signaling molecules. In Part 2 of this newsletter, we will investigate more! As we learn more about the effects of specific amino acids, we can modify a horse’s diet not just for basic calories, but for targeted health, metabolic well-being, and longevity.
We do the best we can for our horses. Understanding our horse's needs is a part of that.
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Disclaimer: Statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease or health condition.
©Joan Kulifay, MSc. 2026