Lyme Disease and Endocrine Dysregulation in Horses

Lyme disease, caused by the bacteria Borrelia burgdorferi and transmitted primarily through tick bites, is a significant health concern for horses. Most horse owners are familiar with the common signs of Lyme disease—shifting lameness, (where the horse appears lame in different legs at different times), behavior changes like sensitivity to touch, irritability, and sometimes neurological symptoms. However, what many people do not realize is that Lyme disease can also affect a horse's endocrine system and blood sugar regulation, in ways that might increase the risk of laminitis.

Lyme disease is an unfortunate part of owning horses in Virginia, where my office is located. However, Lyme disease and its co-infections are on the rise across the country. Even after conventional treatment, Lyme and tick diseases are rarely ever "cured" as the spirochetes that cause them remain in the body, lying dormant indefinitely. Typically, we see horses have "flares" of Lyme in the spring and fall, and often these horses end up on an every-six-months-cycle of antibiotics.

Here we will explore how Lyme disease creates inflammation in the horse's body, how this inflammation disrupts important hormones like cortisol and insulin, and ultimately how these changes can put your horse at higher risk for laminitis. We will also discuss strategies to break the cycle of inflammation and support horses long-term, beyond repeated rounds of (frequently ineffective) antibiotics. By understanding these connections, both veterinarians, horse owners, and other equine healthcare practitioners can work together to identify problems early and take steps to protect horses from these serious complications.

How Lyme Disease Causes Inflammation in Horses

When a tick infected with Lyme bacteria (Borrelia burgdorferi) bites your horse, it injects these bacteria into the bloodstream. Most bacterial infections trigger a strong, immediate immune response that quickly eliminates the invader. However, Lyme bacteria are master escape artists. Think of them as clever criminals who can disguise themselves, hide in hard-to-reach places, and even "play dead" to avoid being caught by the immune system.

The Lyme bacteria use several tricks to evade your horse's immune defenses. They can change their outer surface (like changing disguises)

1. They hide in tissues where the immune system does not work as effectively

2. They can manipulate the horse's immune response

3. They can enter a dormant state where they are barely active and harder to detect

   
   

Because of these evasion tactics, instead of a short-lived infection that is quickly cleared, Lyme creates a long-lasting, almost smoldering inflammation that can persist for months, or even years, if not properly treated and supported. This persistent infection causes the horse's body to produce inflammatory substances called cytokines.

Understanding Cytokines: Lyme Disease Management

Cytokines are specialized proteins made by various types of white blood cells that turn on the immune system to attack invaders like bacteria (for example, Lyme and its co-infections like anaplasmosis, ehrlichia, and rocky mountain spotted fever), intestinal yeast, parasites, viruses, mold, environmental toxins, and heavy metals. In the right amount, they promote healing. In excess, they cause all the major Lyme disease symptoms and dysregulate the immune system.

The problem, particularly in chronic Lyme, is that cytokines are usually produced in excess. Most Lyme symptoms—like sensitivity to touch, fever, stiffness and/or swelling of joints, and behavioral changes—are also symptoms of excess cytokines, often called a "cytokine storm".

How Cytokines Are Produced

Cytokines are made when immune cells are stimulated by germs, toxins, and oxidizing agents. Once the immune cells are activated, an intracellular messenger called NF-kB causes production of cytokines and activates white blood cells. Within these white blood cells, the production of cytokines requires enzymes called kinases which transfer phosphate groups from ATP to specific molecules.

The body's cells also have a genetic messenger called Nrf2 that increases cell production of antioxidants like glutathione. Antioxidants decrease oxidizing agents that trigger cytokine production, so activating Nrf2 creates antioxidants which in turn decrease cytokine production.

Sleep patterns also have a significant impact. Lack of sleep triggers more cytokines, and high cytokine levels can cause anxiety which then interferes with horses getting enough recumbent sleep—creating another vicious cycle.

These inflammatory cytokines are the link between Lyme infection and endocrine disruption, as they begin to affect other body systems—including the hormone (endocrine) system.

How Inflammation Triggers Stress Hormone Production

When your horse's body detects ongoing inflammation, for the purposes of this discussion from Lyme disease, it responds the same way it would to any stressor—by activating a hormone cascade called the "stress response" (this hormonal cascade happens within the hypothalamic-pituitary-adrenal axis or HPA axis). This is like triggering the body's emergency response system.

Here is how it works:

1. Those inflammatory substances (cytokines) we mentioned earlier send distress signals to the brain, specifically to a region called the hypothalamus

2. The hypothalamus sends hormone signals to the pituitary gland (a prune-sized gland at the base of the brain)

3. The pituitary gland then signals the adrenal glands (small glands that sit atop the kidneys)

4. The adrenal glands release cortisol, the body's primary stress hormone

   
   

In normal situations, this stress response is helpful—it is designed to help your horse deal with short-term challenges. Cortisol temporarily increases blood sugar for energy, reduces inflammation, and helps the body manage stress. Once the threat passes, cortisol levels should return to normal.

The problem occurs when Lyme disease causes persistent inflammation, keeping this stress response activated for weeks, months, or even years. It is like keeping your horse's body in a constant state of emergency. Over time, this chronic elevation of cortisol disrupts many normal bodily functions and can result in symptoms such as muscle wasting, immune suppression, and insulin resistance. 

How Stress Hormones Affect Insulin Function

When cortisol stays elevated due to ongoing inflammation, it begins to interfere with another critical hormone: insulin. Insulin is like a key that unlocks cells so they can absorb sugar (glucose) from the bloodstream. This relationship between cortisol and insulin represents the critical link between Lyme disease and increased laminitis risk.

Insulin Resistance: When Cells Stop Listening

Prolonged high cortisol levels cause body tissues to become "resistant" to insulin's effects. Think of it like this: normally, insulin knocks on the door of muscle and fat cells, and they open up to let glucose in. But when cortisol stays high for too long, the cells start ignoring insulin's knocking—they become "insulin resistant."

This happens because cortisol:

• Interferes with the insulin "keys" fitting into their "locks" (receptors) on cells

• Reduces the number of "glucose transporters" (proteins that move glucose into cells)

• Causes the liver to make more glucose even when it is not needed

• Breaks down fat, releasing substances that further block insulin's action

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In a horse with a chronic Lyme infection, this means their muscles and fat tissues become increasingly unresponsive to insulin signals. As cells stop taking up glucose efficiently, the body produces even more insulin to compensate.

High Insulin Levels (Hyperinsulinemia)

As insulin resistance worsens, the pancreas, the organ that produces insulin, works overtime to produce more and more insulin—trying desperately to overcome the resistance and get glucose into cells. This results in abnormally high insulin levels in the blood, a condition called hyperinsulinemia.

Interestingly, most horses with this condition maintain normal glucose levels despite having very high insulin levels, though your primary care veterinarian will test both insulin and glucose prior to diagnosis. It is important to keep in mind this is very different from diabetes in humans where glucose balance is the issue.

How High Insulin Levels Lead to Laminitis

Research has clearly shown that high insulin levels can trigger laminitis. Let's explore how this happens.

Normally, insulin helps control blood flow by balancing blood vessel dilation (widening) and constriction (narrowing), called vasodilation. It does this by influencing the production of nitric oxide, which helps vessels relax and widen.

However, in insulin resistant horses, this balance gets disrupted. The vessels do not dilate properly, but they still respond to signals that make them constrict. This imbalance can reduce blood flow to the sensitive tissues in the hoof, potentially causing damage due to insufficient blood supply—like a mini "stroke" in the hoof tissues.

Direct Damage to Hoof Laminae

The sensitive laminae in your horse's hooves, the tissue connections that suspend the coffin bone within the hoof, have a large number of IGF-1 receptors on their cells. IGF-1 receptors are protein structures on cell surfaces that receive growth signals, telling the cell when to grow, develop, and repair tissue in your horse's body. Insulin can bind to these IGF-1 receptors and stimulate them, leading to changes in the laminae that contribute to laminitis. 

When insulin levels stay abnormally high, it triggers a series of harmful changes:

• Abnormal cell growth and division in the hoof tissue

• Weakening of the basement membrane (a critical supportive structure)

• Activation of enzymes that break down connective tissue

• Weakening of the cellular attachments that keep the coffin bone suspended

  
  

These changes weaken the critical connections within the hoof, making them more likely to fail under the normal stresses of standing and moving—leading to the coffin bone rotating or sinking, which is what typically happens during a laminitic event.

A Vicious Cycle of Inflammation

Perhaps most concerning is that this entire process creates a dangerous feedback loop. The Lyme infection causes inflammation, which raises cortisol, which causes insulin resistance and high insulin. But then:

• Fat tissue affected by insulin resistance releases even more inflammatory substances

• These new inflammatory substances trigger more cortisol release

• Higher cortisol worsens insulin resistance

• Insulin resistance leads to even higher insulin levels

  
  

This self-perpetuating cycle explains why horses with untreated Lyme disease may develop metabolic problems that can persist even after the infection is addressed—the body gets caught in this inflammatory loop.

Recognizing When Your Horse Might Be Affected

For horse owners, veterinarians, and equine healthcare providers identifying this connection between Lyme disease and hormonal disruption requires careful observation. Here are warning signs that your horse might be experiencing this problem:

1. Unexpected metabolic changes - A horse that suddenly becomes an "easy keeper" or gains a significant amount of weight, despite being an average or “hard keeper” before

2. Changes in fat distribution - Abnormal fat deposits appearing along the crest of the neck, over the shoulders, at the tailhead, or above the eyes, even if the horse isn't overweight overall

3. Abnormal sweating patterns - Patchy sweating or reduced sweating ability

4. Increased drinking and urinating - Without other obvious causes like medication or hot weather

5. Slow-healing wounds - Cuts or scrapes that take longer than normal to heal

6. Frequent hoof problems - Recurring abscesses, unusual growth rings on the hoof wall, or changes in hoof quality

7. Mysterious lameness - Mild lameness that shifts from leg to leg and comes and goes

   
   

If you notice these signs in a horse with a history of Lyme disease, or in an area where Lyme is common – which is essentially everywhere in the United States, talk to your veterinarian about testing not just for hormonal imbalances but also for Lyme and tickborne diseases.

Testing might include:

-            Blood tests for resting insulin levels

-            Dynamic testing (how the horse's insulin responds to sugar)

-            Testing for ACTH (another hormone that can be affected), standing ACTH should be sufficient

-            Blood tests for inflammatory markers and subtle signs of ongoing infection, usually via CBC/Chem

-            4DX SNAP Test to screen for tick diseases

-            Lyme Multiplex or complete tick disease panels

Prevention and Management: Protecting Your Horse

The best way to avoid this whole chain of complications is to prevent Lyme disease in the first place:

• Check your horse for ticks daily, especially in tick-prone areas

• Use appropriate tick repellents, but avoid toxic chemicals and pesticide topicals

• Manage your property to reduce tick habitats (keep grass short, remove leaf litter, keep trees cut back)

• Remove any attached ticks promptly and correctly (using tweezers close to the skin)

Monitoring Hormones After Lyme Disease

For horses that have had Lyme disease, hormonal monitoring should become part of their regular healthcare:

• Ask your vet about testing insulin and metabolic levels as well as screening for reinfection and/or chronic lyme infection titers

• Monitor for changes in body shape and fat deposits

• Check your horse’s hooves for any early warning signs of problems like rings in the hoof horn or red to reddish purple bruising on their soles or stretching of the white line.

Diet and Management Adjustments

If your horse has had Lyme disease, these management strategies can help protect against insulin problems and laminitis:

• Feed a diet low in sugars and starches (non-structural carbohydrates or NSCs)

• Eliminate feed items and treats containing conventional soy, wheat and wheat by-products, corn, molasses, and canola products

• Use hay testing to identify forage with lower NSC content (ideally below 10-12%)

• Provide good-quality protein sources like sainfoin, hemp hearts, or chia seeds

• Talk to your equine nutrition professional about magnesium and chromium supplementation, which may help improve insulin sensitivity

• Maintain a regular exercise program appropriate to your horse's condition

• Be extra cautious about pasture access during high-risk times (spring and fall when the sugar content of grass is highest)

• Keep your horse at a healthy weight

Long-Term Support: Getting Horses Off the "Antibiotic Carousel"

While antibiotics can be important for addressing active infection, they do not usually eliminate the Lyme bacteria, and they do not address the ongoing inflammatory cascade that can continue or even be exacerbated after treatment. A more comprehensive approach focuses on reducing inflammation at its source while supporting the horse's own regulatory systems.

Here are essential strategies for long-term management of horses with chronic Lyme disease and its endocrine effects:

1. Reduce/Eliminate Parasites and Mold Toxicity

Both intestinal parasites and exposure to mold toxins can further stimulate immune responses and cytokine production. Regular, appropriate deworming protocols based on fecal testing are essential. Additionally, check hay, feed, and bedding for mold, and ensure barn areas have good ventilation to prevent mold growth.

2. Increase Antioxidants

Antioxidants help neutralize the oxidizing agents that trigger cytokine production.

3. Increase Nrf2 Activation

Nrf2 is the body's master regulator of antioxidant production.

4. Block Kinase Enzymes

Since kinase enzymes are needed for cytokine production, inhibiting these enzymes can help reduce inflammation.

5. Provide Clean, Quality Vitamin/Mineral Supplementation

Proper mineral balance is essential for immune function and endocrine health.

Keep in mind that all forms of vitamins and minerals are not equal. Do your research on the most bio-available forms, or ideally, work with a functional equine nutrition professional.

6. Promote Sleep

Horses need approximately thirty minutes of recumbent (lying down) sleep each day for proper rest and immune function. To support healthy sleep:

• Provide a safe, quiet environment where horses feel secure enough to lie down

• Ensure adequate bedding that is comfortable for lying down

• Allow for social stability with compatible herd mates

• Maintain regular routines to reduce stress

  
  

7. Feed a Species Appropriate, Nutrient-Dense, Real Foods Diet

The foundation of all health management for horses with Lyme disease and endocrine issues should be a diet that:

• Is based primarily on forage

• Limits processed feeds

• Includes natural sources of vitamins and minerals

• Supports gut health through biome foods

• Matches the horse's actual energy needs to prevent obesity

Key Takeaways

Lyme disease affects more than just your horse's joints and nervous system—it can set off a chain reaction that impacts their entire hormonal balance. The persistent inflammation caused by Lyme bacteria triggers increased cortisol (stress hormone) production, which in turn leads to insulin resistance and abnormally high insulin levels. These high insulin levels can directly damage the sensitive tissues in the hoof, potentially resulting in laminitis.

What makes this connection particularly important is that these hormonal changes can develop gradually and persist even after the initial Lyme infection appears to be resolved. A horse might seem to recover from Lyme disease, only to develop metabolic problems and laminitis months, or even years later.

The chronic nature of Lyme disease presents a significant challenge. Even after conventional antibiotic treatment, the spirochetes that cause Lyme can remain dormant in the body indefinitely, leading to seasonal flare-ups (typically in spring and fall) and an ongoing cycle of antibiotic treatments that may never fully resolve, and in fact, may worsen the underlying condition.

The key to breaking this cycle lies in addressing the root cause—inflammation driven by cytokines—rather than just treating symptoms. By understanding and implementing the strategies outlined above, horse owners, veterinarians, and other equine healthcare practitioners can help affected horses maintain better health with fewer flare-ups, reduce the need for repeated rounds of (frequently ineffective) antibiotics, and protect them from secondary complications like laminitis.

This integrative approach—combining appropriate medical care with strategic dietary management of inflammation—offers the best hope for horses living with chronic Lyme disease and its potentially life-threatening endocrine effects.

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Getty, J. M. (2013). Equine Cushing's disease: Nutritional management (Spotlight on Equine Nutrition, Vol. 6). CreateSpace Independent Publishing Platform.

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Perlmutter, D. (2015). Brain maker: The power of gut microbes to heal and protect your brain for life. Little, Brown Spark.

Warren, K., & Deglmann, P. (n.d.). Comprehensive guide to treating chronic Lyme disease and co-infections in Minnesota: Evidence-based protocols. LymeDr. https://www.lymedr.com/home