In the last couple of newsletters, we covered various amino acids that act as signaling molecules (Part 1 here, Part 2 here). This week, we will cover the very important, but often overlooked amino acid: Glycine.
◆︎ Glycine as a Signaling Molecule
Glycine is the smallest amino acid in existence, but it has incredibly important roles. As a signaling molecule, one of its main jobs involves neuroreceptors and pain pathways in the central nervous system.
Glycine’s effect on nerve transmission is to increase the threshold at which a nerve fires—a process called hyperpolarization. By increasing the threshold, the nerve requires a much larger stimulus to fire. This makes small, background stimuli inconsequential, essentially turning down the "volume" of the nervous system. Here are some examples of how this affects the horse:
➡ Muscle spasms, tying-up, and muscle recovery:
Glycine can help reduce muscle spasms by causing the motor neurons to become “stubborn” and fire less readily. This causes the spastic muscle to release and relax. Using glycine on a regular basis may help prevent episodes of tying-up (Exertional Rhabdomyolysis). It is also highly helpful for a horse experiencing tight, sore muscles after a heavy workout.
➡ Calming a hyper-reactive horse:
Because glycine is such a small molecule, it easily crosses the blood-brain barrier. Once in the brainstem, it has the same hyperpolarizing effect—raising the threshold at which nerves fire. Horses are often spooky and reactive due to excitatory neurotransmitters flooding the central nervous system.Glycine helps calm a spooky horse by buffering these signals, and it does so without sedating the horse. This is an excellent tool for horses that need to remain calm during stall-rest and injury recovery, or for the horse that is overly spooky out on the trail.
➡ Chronic pain:
Just as glycine raises the firing threshold to stop muscle spasms, it also raises the threshold for horses dealing with chronic pain (such as chronic hoof pain, arthritis, or an old injury). By dampening the signal as it travels up the spinal cord, glycine provides an element of central pain relief. While glycine slows the nerves from firing, it does not affect the localized COX-2 inflammatory pathway the way traditional NSAIDs (like Bute or Equioxx) do. This makes glycine a perfect, safe adjunct to use alongside other pain medications and supplements.
◆︎ Glycine as a Critical Component of Collagen
Beyond its role as a signaling molecule, glycine is an indispensable structural protein. It is the fundamental building block of connective tissue, which is made of collagen. Collagen is a tightly twisted triple-helix, and for it to twist properly, every third amino acid in the chain must be glycine.
Types of injuries and situations that heavily benefit from additional glycine:
- Tendons and Ligaments:Glycine is especially important in the treatment of bowed tendons, suspensory ligament injuries, and deep digital flexor tendon (DDFT) tears. The repair of these tissues requires a massive amount of collagen, making supplemental glycine a critical raw material for healing.
- Skin Injuries:Skin repair relies heavily on collagen. Glycine supports the healing of severe lacerations, proud flesh, pastern dermatitis (scratches), and even genetic conditions like HERDA.
- Bone Injuries: Laying down new bone matrix requires a significant amount of collagen. Typical situations that benefit from additional glycine include fractures, arthritis, bucked shins, and sesamoiditis.
◆︎ Glycine’s Protective Role for SGLT2 Inhibitors
When a horse is prescribed an SGLT2 inhibitor (like ertugliflozin) to help lower dangerously high insulin levels, the drug forces glucose to be dumped into the urine. With this sudden drop in blood sugar, the horse’s body switches to burning body fat for energy.
However, this rapid oxidation of fat creates toxic intermediate organic acids. Glycine acts as a metabolic rescue agent—it physically binds to these toxic acids, making them non-toxic and water-soluble so they can be safely flushed out of the body in the urine. This process saves the liver from hepatic lipidosis and prevents metabolic collapse.
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◆︎ Serving Size Information
While we look to much higher serving sizes for horses on SGLT2 inhibitors (100 grams per day), the amounts are more modest for horses with other issues.
- General Calming or Muscle Relief: 20-30 grams per day.
- Tendon, Bone, or Skin Injuries: 30-40 grams per day.
Administration Tip: It is always best to split these doses into twice-daily feedings (e.g., morning and night) to help the horse maintain a steady state of glycine in their system.
Why the massive dose for SGLT2 inhibitors?
The higher dose is required because the horse's body is constantly mobilizing fats. Binding the toxic intermediates is an ongoing, daily crisis. You must have plenty of glycine "on board" so that no matter how many toxic acids are created, there is always a free glycine molecule waiting to bind to it.
The margin of safety with glycine is exceptionally high. If you feed more glycine than the liver needs, the body simply uses the excess for other tasks, such as to build collagen, create glutathione, create creatine, or safely clears it in the urine.
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