Up to 90% of horses treated for gastric ulcers with omeprazole can experience a recurrence of ulcers when they stop taking this drug.
Horses can develop rebound acid hypersecretion (RAHS) after the discontinuation of omeprazole. Higher levels of stomach acid often lead to new ulcers being formed, particularly if the underlying causes of ulceration have not been addressed.
This is frustrating for both horse owners and veterinarians, leading to reduced performance and well-being in the horse. Why do so many horses experience ulcer rebound and what can be done to prevent these gastric lesions from coming back?
Some performance horses are maintained on omeprazole year-round to reduce the risk of recurrence.
But long-term omeprazole use is not advised because this drug can interfere with the digestibility and absorption of certain nutrients in the diet. Keeping a horse on omeprazole is also an expensive proposition.
Instead, you can prevent ulcer relapse in your horse by supporting their gut health, identifying risk factors, and adopting research-backed feeding and management practices.
Omeprazole for Ulcer Treatment
GastroGard, a slow-release form of omeprzole, is the only FDA-approved treatment to resolve and prevent gastric ulcers in horses. Due to the high prevalence of Equine Gastric Ulcer Syndrome (EGUS) in performance and pleasure horses, the use of this drug is widespread.
Omeprazole is a proton pump inhibitor that works by decreasing the production of stomach acid. By raising the gastric pH (lowering stomach acidity), omeprazole creates a more favourable environment to allow existing ulcers to heal.
Although omeprazole treatment is effective at resolving existing ulcers in the squamous region of the stomach, it is not a long-lasting effect. Omeprazole needs to be given continuously to inhibit the secretion of gastric juices.
Evidence of Ulcer Rebound in Horses
These studies demonstrate that 4 mg/kg of omeprazole given daily is effective in reducing ulcer number and severity. However, when treatment is stopped, ulcers are likely to form again.
In one study, 90% of horses had a recurrence of ulcers after being taken off of the 4 mg/kg daily dose of omeprazole. 
To avoid this, some veterinarians recommend gradually reducing the dose to 1 or 2 mg/kg after 28 days. However, even with this strategy, 16-20% of horses develop new lesions or worsening lesions during the period of reduced omeprazole dosing. 
Furthermore, performance horses that are most at risk of ulcer rebound may not be able to use omeprazole continuously.
Competitions require that horses undergo a 72-hour withdrawal period from this drug prior to competition. This could be enough time for ulceration to occur. 
Careful attention needs to be paid to horses discontinuing omeprazole use. There are strategies you can use to reduce the risk of ulcer rebound, which we will discuss later on in this article.
Why Do Ulcers Come Back in Horses?
This question is still an active area of research. However, the following mechanisms have been hypothesized to contribute to the high rates of ulcer recurrence in horses.
Rebound Acid Hypersecretion
After cessation of omeprazole treatment, rebound gastric hyperacidity and ulcer recurrence are common.
Gastric acid production occurs in parietal cells of the stomach, which secrete acid in response to several signals including histamine and the hormone gastrin.
Gastrin is secreted in response to a meal and triggers histamine secretion from enterochromaffin-like (ECL) cells in the stomach. Together histamine and gastrin stimulate parietal cells to produce stomach acid.
When acid is secreted and gastric pH decreases, a negative feedback loop turns off gastrin secretion. 
Omeprazole works by inhibiting the final step of acid production in parietal cells. This increases gastric pH which allows gastrin production to rise. Gastrin also triggers the proliferation of ECL cells that produce histamine.
Once treatment with omeprazole is discontinued and acid secretion is no longer blocked, the parietal cells respond to higher levels of gastrin and histamine by secreting more acid. The result is a hyper-acidic environment, which can lead to new lesions in the stomach lining. 
Although these mechanisms have mostly been shown in humans and animal models, horses treated with 4 mg/kg of omeprazole per day had a two-fold increase in gastrin levels after 14 days.  This suggests similar mechanisms could be occurring in horses.
Decreased Efficacy Over Time
Another possible explanation for ulcer recurrence during and after omeprazole treatment is a loss of efficacy over time.
One study showed that the ability of omeprazole to completely heal ulcers decreased over time when 4 mg/kg of daily omeprazole was continued for 90 days.
The percentage of horses with squamous ulcers that showed complete healing at 30 days was 29%. This dropped to just 11% of horses showing complete healing at 90 days. 
Potential reasons for decreased efficacy over time include reduced owner compliance and upregulation of omeprazole breakdown. In horses given 4 mg/kg daily, the bioavailability (measured as total circulating amount) decreased by 50% after 29 days. 
Omeprazole is catabolized via hepatic cytochrome 450 in other animals and this process is upregulated with ongoing treatment. 
The cytochrome 450 pathway is used to catabolize many xenobiotics. This is not only a concern for omeprazole bioavailability but also the efficacy of other drugs or therapeutics that are given concomitantly.
If environmental or dietary factors that caused the ulcers in the first place have not been addressed, ulcers are likely to come back once omeprazole treatment is stopped.
Common causes of ulcers include:
- Intermittent feeding
- High intensity exercise, particularly on an empty stomach
- Feeding large quantities of grain
- Limited access to water
- Trailering and changes in environment
- Changes in social grouping
- High levels of stress
The best way to reduce your horse’s ulcer risk is to ensure they have continuous access to forage and water, limit their stress, never exercise on an empty stomach, and avoid intense competition schedules.
For some high-level performance horses, it may not be possible to decrease their training schedules. This can lead to many horses being maintained on long-term omeprazole treatment at a lower dose to prevent gastric ulcers in performance horses that
However, ongoing research suggests that omeprazole may not be suitable for long-term use. It can have unintended effects on digestion and metabolism and may increase fracture risk.
Other Concerns with Omeprazole Use
Ulcer rebound is a major concern when a horse is put on omeprazole, but keeping your horse on this drug may not be the best strategy. Not only is omeprazole expensive, it has been observed to cause negative effects in other animals and horses including:
- Reduced digestibility of protein
- Decreased absorption of minerals, incluing calcium and magnesium
- Increased fracture risk
- Increased risk of colic when given along with bute
Effects on Digestion and Metabolism
Omeprazole maintains a less acidic gastric environment for up to 16 – 18 hours after administration.  While this may be beneficial for ulcers, reducing acidity in the stomach can negatively affect the digestion of feed.
Gastric acids are required to activate enzymes that initiate the processes of protein and carbohydrate digestion. In a less acidic environment, activation of these enzymes is impaired, which can affect the digestion of protein and carbohydrates in the foregut.
If too much protein and carbohydrate reaches the hindgut, it can lead to hindgut acidosis.
Research shows that omeprazole treatment for 11 days alters biomarkers of lipid, protein and mineral digestion in horses. This includes increased plasma cholesterol, decreased magnesium and decreased phosphorus levels. 
In another study, calcium digestibility was negatively affected by omeprazole treatment. 
Increased Fracture Risk
Humans taking omeprazole are observed to have an increased fracture risk when on this drug. The proposed mechanisms include hypergastrinemia (elevated gastrin levels) and decreased absorption of calcium, magnesium and vitamin B12. 
The effects of long-term omeprazole use on bone mineral density or fracture rate have not been established in horses, but there is concern that it may negatively affect bone mineralization.
In horses, omeprazole treatment has been shown to induce hypergastrinemia and decreased absorption of minerals that are important for bone health.
Vitamin B12 absorption occurs in the hindgut of horses, which is unlikely to be affected by omeprazole treatment and is unlikely to be a factor in fracture risk in horses.
Although this was evaluated in only a small group of horses, it suggests caution should be taken when prescribing the NSAID phenylbutazone to a horse on omeprazole or vice versa.
This increased risk may be related to changes in the microbiome, intestinal motility, intestinal inflammation and/or ulceration. 
How to Prevent Ulcers from Recurring
If your horse is ready to come off omeprazole for the treatment of gastric ulcers, it is important to take preventative steps to reduce the risk of ulcer recurrence.
Preventing ulcer rebound involves making changes to dietary and management factors that are likely to contribute to the development of this condition.
The use of suitable gut health supplements can also reduce ulcer recurrence and minimize the reliance on omeprazole.
- Feeding small meals more frequently during the day
- Reducing overall starch and sugar content of the diet
- Decreasing starch and sugar content of individual meals
- Allowing constant access to forage and increased turnout on pasture
- Providing adequate protein in the diet
- Using fats to increase energy density of diet if needed
- Encouraging water intake with free-choice access to water and salt
- Feeding the horse prior to exercise
Some management issues also contribute to ulcer risk, particularly if they contribute to stress in your horse. The following stressors have been identified in horses:
- Changes in herd dynamics
- Decreased turn out time
- Poor acclimitization to trailering
- Irregular feeding or light schedules
- Poor environmental enrichment
- Management issues that contribute to stereotypical behaviours, which can limit feed intake
Supplements to Support Gastric Health
Once nutrition and management factors have been addressed, consider feeding a gastric health supplement to support the stomach lining when discontinuing omeprazole.
Mad Barn’s Visceral+ has been clinically tested in horses being weaned off omeprazole.
Horses were treated with Gastroguard for 15 – 39 days and then were given Visceral+ starting one to two weeks before omeprazole cessation. Visceral+ was continued for 30 days following omeprazole treatment.
All horses fed Visceral+ showed improvement or complete healing when they were re-scoped at 60 days.
Visceral+ does not interfere with gastric acid production and does not negatively affect digestion or lead to rebound hyperacidity.
Instead, Visceral+ contains ingredients to maintain gastric and hindgut health and support the immune system.
The following research-backed ingredients are found in Visceral+ and contribute to gastric health:
- Dietary nucleotides
The horse’s gut uses up to 33% of circulating glutamine to provide energy for digestive processes including mucus production, nutrient utilization and tissue repair. 
Other systems in the horse’s body – including the immune system – have high glutamine requirements as well. Infections, exercise and stress decrease circulating glutamine in horses, limiting its availability for use in the gut. 
Glutamine is often included in equine gut health supplements. However, it needs to be provided at adequate levels to appreciably increase plasma glutamine levels and supply to the intestine. 
Lecithin is a phospholipid derived from plants. In the squamous region of the stomach, it forms a phospholipid barrier between gastric acid and the stomach lining.
Mannan-oligosaccharides are oligosaccharides derived from yeast and plants.
Mannan-oligosaccharides modulate several aspects of tissue repair processes, including: 
- The immune response in the gut
- Mucin production by goblet cells
- Secretory immunoglobulin A production
- Microbial attachment to intestinal epithelial cells
Nucleotides are required for the maturation of new cells in the digestive tract. Cells in the gastrointestinal tract have a high turnover rate and a high requirement for nucleotides.
Although these can be synthesized within the body, adding sources of nucleotides to the diet helps reduce reliance on endogenous production.
Supplementation with dietary nucleotides has been shown to support gastrointestinal growth and maturation and recovery from intestinal injury. 
Dietary nucleotides also enhance mucosal height and gut wall thickness to improve the absorption of nutrients from the gut. 
Rates of ulcer recurrence are very high when stopping omeprazole treatment. However, there are ways that you can support your horse’s gut health and decrease the risk of gastric ulcer rebound.
Mad Barn’s Visceral+ is a comprehensive gut health supplement that includes lecithin, glutamine, nucleotides and mannan-oligosaccharides to support gastric and intestinal health. It also supports hindgut function with high inclusion of prebiotics, probiotics and yeast.
For best outcomes, Visceral+ should be added to a balanced diet that meets the horse’s vitamin and mineral requirements, provides minimal starch and sugars, and free-choice access to suitable forages.
To evaluate your horse’s diet, submit their information online to our equine nutritionists who can help you develop a feeding program that supports ulcer recovery and decreases the risk of rebound.
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